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Sample records for characterizing pulmonary blood

  1. Characterizing pulmonary blood flow distribution measured using arterial spin labeling.

    PubMed

    Henderson, A Cortney; Prisk, G Kim; Levin, David L; Hopkins, Susan R; Buxton, Richard B

    2009-12-01

    The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.

  2. Modelling pulmonary blood flow.

    PubMed

    Tawhai, Merryn H; Burrowes, Kelly S

    2008-11-30

    Computational model analysis has been used widely to understand and interpret complexity of interactions in the pulmonary system. Pulmonary blood transport is a multi-scale phenomenon that involves scale-dependent structure and function, therefore requiring different model assumptions for the microcirculation and the arterial or venous flows. The blood transport systems interact with the surrounding lung tissue, and are dependent on hydrostatic pressure gradients, control of vasoconstriction, and the topology and material composition of the vascular trees. This review focuses on computational models that have been developed to study the different mechanisms contributing to regional perfusion of the lung. Different models for the microcirculation and the pulmonary arteries are considered, including fractal approaches and anatomically-based methods. The studies that are reviewed illustrate the different complementary approaches that can be used to address the same physiological question of flow heterogeneity.

  3. A Blood-Based Proteomic Classifier for the Molecular Characterization of Pulmonary Nodules

    PubMed Central

    Li, Xiao-jun; Hayward, Clive; Fong, Pui-Yee; Dominguez, Michel; Hunsucker, Stephen W.; Lee, Lik Wee; McLean, Matthew; Law, Scott; Butler, Heather; Schirm, Michael; Gingras, Olivier; Lamontagne, Julie; Allard, Rene; Chelsky, Daniel; Price, Nathan D.; Lam, Stephen; Massion, Pierre P.; Pass, Harvey; Rom, William N.; Vachani, Anil; Fang, Kenneth C.; Hood, Leroy; Kearney, Paul

    2014-01-01

    Each year millions of pulmonary nodules are discovered by computed tomography and subsequently biopsied. As the majority of these nodules are benign, many patients undergo unnecessary and costly invasive procedures. We present a 13-protein blood-based classifier that differentiates malignant and benign nodules with high confidence, thereby providing a diagnostic tool to avoid invasive biopsy on benign nodules. Using a systems biology strategy, 371 protein candidates were identified and a multiple reaction monitoring (MRM) assay was developed for each. The MRM assays were applied in a three-site discovery study (n = 143) on plasma samples from patients with benign and Stage IA cancer matched on nodule size, age, gender and clinical site, producing a 13-protein classifier. The classifier was validated on an independent set of plasma samples (n = 104), exhibiting a high negative predictive value (NPV) of 90%. Validation performance on samples from a non-discovery clinical site showed NPV of 94%, indicating the general effectiveness of the classifier. A pathway analysis demonstrated that the classifier proteins are likely modulated by a few transcription regulators (NF2L2, AHR, MYC, FOS) that are associated with lung cancer, lung inflammation and oxidative stress networks. The classifier score was independent of patient nodule size, smoking history and age, which are risk factors used for clinical management of pulmonary nodules. Thus this molecular test can provide a powerful complementary tool for physicians in lung cancer diagnosis. PMID:24132637

  4. Determinants of pulmonary blood volume

    PubMed Central

    Lewis, Milena L.; Gnoj, Julian; Fisher, Vincent J.; Christianson, Lynn C.

    1970-01-01

    Pulmonary blood volume was determined by the radiocardiographic technique in 49 patients coming to cardiac catheterization. Since this method has not been directly compared with the more commonly used double injection of dye. 25 comparisons were carried out in 13 patients of the series. Agreement was good over a range of 4.5-21.1 heart cycles since there was no statistically significant difference between transit time values measured by the two methods. The relation of pulmonary blood volume to other hemodynamic factors in these 49 patients, with and without cardiac or pulmonary disease, was evaluated by means of multiple regression analysis. The analysis carried out for mean transit time indicates that this parameter varies predominately with flow. Pulmonary blood volume, in this series of resting recumbent individuals, varies to a significant degree only with total blood volume and with pulmonary venous pressure. No parameters of vascular distensibility, such as pulmonary vascular resistance, were found to affect the volume of blood in the lungs. The fact that variations in pulmonary blood volume among the subjects could be described by a multiple regression equation linear with respect to total blood volume and pulmonary venous pressure indicates that these variations are the result of passive distention of components of the vascular bed. PMID:4902826

  5. Vascular structure determines pulmonary blood flow distribution

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Glenny, R. W.

    1999-01-01

    Scientific knowledge develops through the evolution of new concepts. This process is usually driven by new methodologies that provide observations not previously available. Understanding of pulmonary blood flow determinants advanced significantly in the 1960s and is now changing rapidly again, because of increased spatial resolution of regional pulmonary blood flow measurements.

  6. Vascular structure determines pulmonary blood flow distribution

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Glenny, R. W.

    1999-01-01

    Scientific knowledge develops through the evolution of new concepts. This process is usually driven by new methodologies that provide observations not previously available. Understanding of pulmonary blood flow determinants advanced significantly in the 1960s and is now changing rapidly again, because of increased spatial resolution of regional pulmonary blood flow measurements.

  7. Isolation and Characterization of Two Novel Bacteria Afipia cberi and Mesorhizobium hominis from Blood of a Patient Afflicted with Fatal Pulmonary Illness

    PubMed Central

    Lo, Shyh-Ching; Li, Bingjie; Hung, Guo-Chiuan; Lei, Haiyan; Li, Tianwei; Zhang, Jing; Nagamine, Kenjiro; Tsai, Shien; Zucker, Mark J.; Olesnicky, Ludmilla

    2013-01-01

    We recently isolated and discovered new Bradyrhizobiaceae microbes from the cryopreserved culture broth of blood samples from 3 patients with poorly defined illnesses using modified SP4 media and culture conditions coupled with genomic sequencing. Using a similar protocol, we studied a previously cryopreserved culture broth of blood sample from a patient who had succumbed to an acute onset of fulminant pulmonary illness. We report that two phases of microbial growth were observed in the re-initiated culture. Biochemical and genomic characterization revealed microbes isolated from the first phase of growth were new Afipia species of Bradyrhizobiaceae, tentatively named A. cberi with a ~ 5 MB chromosome that was different from those of all previously known Afipia microbes including the newly discovered A. septicemium. The microbes isolated from the second phase of growth were prominent sugar assimilators, novel Phyllobacteriaceae, phylogenetically most closely related to Mesorhizobium and tentatively named M. hominis with a ~ 5.5 MB chromosome. All A. cberi isolates carry a circular ~ 140 KB plasmid. Some M. hominis isolates possess a circular ~ 412 KB plasmid that can be lost in prolonged culture or passage. No antibiotics resistant genes could be identified in both of the A. cberi and M. hominis plasmids. Antibiotic susceptibility studies using broth culture systems revealed isolates of A. cberi could be sensitive to some antibiotics, but all isolates of M. hominis were resistant to essentially all tested antibiotics. However, the cell-free antibiotics susceptibility test results may not be applicable to clinical treatment against the microbes that are known to be capable of intracellular growth. It remains to be determined if the 2 previously unknown Rhizobiales were indeed pathogenic and played a role in the pulmonary disease process in this patient. Specific probes and methods will be developed to re-examine the diseased lungs from patient's autopsy. PMID

  8. Pulmonary blood flow distribution after banding of pulmonary artery.

    PubMed Central

    Samánek, M; Fiser, B; Ruth, C; Tůma, S; Hucín, B

    1975-01-01

    Radioisotope lung scanning was used to investigate the distribution of pulmonary blood flow after banding of the pulmonary artery in children with a left-to-right shunt and pulmonary hypertension. An abnormal distribution of blood flow in the lung on the side of the operation approach was observed in all patients in the first three weeks following surgery. Abnormalities were still observed in 17 of 21 children 10 months to more than 8 years after the banding operation. There was no significant relation between the occurrence of these abnormalities and time after surgery. Diminished flow to the zones of the right lung was observed less frequently. The incidence of abnormalities in flow distribution was also high preoperatively. Respiratory complications in infants with large left-to-right shunts were considered to be responsible for most of the abnormal blood flow distributions observed. Radioactive lung scanning was found to be a valuable diagnostic method in the early and late postoperative period in infants and small children. It was more sensitive than the other techniques used in revealing deviation of blood flow from one lung in those cases with shifting of the applied band. Images PMID:1111558

  9. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

    PubMed

    Jiang, Chunling; Qian, Hong; Luo, Shuhua; Lin, Jing; Yu, Jerry; Li, Yajiao; An, Qi; Luo, Nanfu; Du, Lei

    2017-05-01

    Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

  10. Measuring blood delivery to solitary pulmonary nodules using perfusion magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Wang, Zhifeng; Shen, Li; Gao, Ling; Ford, James C.; Makedon, Fillia S.; Pearlman, Justin D.

    2006-03-01

    With perfusion magnetic resonance imaging (pMRI), perfusion describes the amount of blood passing through a block of tissue in a certain period of time. In pMRI, the tissue having more blood passing through will show higher intensity value as more contrast-labeled blood arrives. Perfusion reflects the delivery of essential nutrients to a block of tissue, and is an important parameter for the tissue status. Considering solitary pulmonary nodules (SPN), perfusion differences between malignant and benign nodules have been studied by different techniques. Much effort has been put into its characterization. In this paper, we proposed and implemented extraction of the SPN time intensity profile to measure blood delivery to solitary pulmonary nodules, describing their perfusion effects. In this method, a SPN time intensity profile is created based on intensity values of the solitary pulmonary nodule in lung pMRI images over time. This method has two steps: nodule tracking and profile clustering. Nodule tracking aligns the solitary pulmonary nodule in pMRI images taken at different time points, dealing with nodule movement resulted from breathing and body movement. Profile clustering implements segmentation of the nodule region and extraction of the time intensity profile of a solitary pulmonary nodule. SPN time intensity profiles reflect patterns of blood delivery to solitary pulmonary nodules, giving us a description of perfusion effect and indirect evidence of tumor angiogenesis. Analysis on SPN time intensity profiles will help the diagnosis of malignant nodules for early lung cancer detection.

  11. [Detection and characterization of pulmonary nodules using multislice computed tomography].

    PubMed

    Bastarrika, G; Cano, D; Hernández, C; Alonso-Burgos, A; González, I; Villanueva, A; Vivas, I; Zulueta, J

    2007-01-01

    Pulmonary nodules are a common finding in routine chest studies. Although there are no pathognomic clinical or radiological signs that enable the exact nature of a pulmonary nodule to be determined, the clinical context and the appropriate characterization of the pulmonary nodule make it possible to reach the correct diagnosis in most cases. This article discusses the most important aspects involved in the use of multislice computed tomography in the noninvasive detection and characterization of pulmonary nodules.

  12. Cardiovascular and blood coagulative effects of pulmonary zinc exposure

    SciTech Connect

    Gilmour, Peter S.; Nyska, Abraham; Schladweiler, Mette C.; McGee, John K.; Wallenborn, J. Grace; Richards, Judy H.; Kodavanti, Urmila P. . E-mail: kodavanti.urmila@epa.gov

    2006-02-15

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 {mu}g/kg (2 {mu}mol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1-24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.

  13. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  14. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  15. Abnormal distribution of pulmonary blood flow in aortic valve disease

    PubMed Central

    Goodenday, Lucy S.; Simon, George; Craig, Hazel; Dalby, Lola

    1970-01-01

    Wasted ventilatory volume (VD) and its ratio to tidal volume (VD/VT) were measured at rest and during exertion in 17 patients with aortic valve disease. We considered VD/VT to indicate abnormal ventilation: perfusion relations if it did not decrease on exertion, or if the exercising value was greater than 40 per cent. Plain chest radiographs were independently examined for evidence of diversion of pulmonary blood to the upper lobes. There was significant agreement (p<0·05) between radiographic and pulmonary function estimations of abnormality. This suggests that the raised pulmonary venous pressure associated with left ventricular failure creates an abnormal pattern of blood flow through the lung, which is responsible for causing inadequate perfusion with respect to ventilation. Images PMID:5420086

  16. The value of dual-source multi detector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.

    PubMed

    Chaosuwannakit, Narumol; Makarawate, Pattarapong

    2017-07-13

    Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). CA is considered the gold standard for delineation of anatomy in children with pulmonary atresia with ventricular septal defect (PA with VSD). Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA with VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty eight patients with PA with VSD were underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, MAPCAs and type of blood supply (dual versus single supply) were evaluated by a blinded experts and results were compared with CCA. 28 patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and three patients had stenosis of distal branches of pulmonary arteries; all had major aortopulmonary collateral arteries (MAPCAs) from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity,positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover accuracy of detecting MAPCAs were excellent. These results suggest that MDCT and CCA are equilavent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allow precise characterization of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD.

  17. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

    PubMed Central

    Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

    2013-01-01

    Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

  18. Effective pulmonary blood flow in normal children at rest.

    PubMed Central

    Bowyer, J J; Warner, J O; Denison, D M

    1988-01-01

    Effective pulmonary blood flow was measured with a soluble inert gas uptake method (10% argon, 3.5% freon-22, 35% oxygen, balance nitrogen) in 98 apparently healthy children aged 5-14 years. None had any evidence of cardiorespiratory disease and all had normal values for absolute and dynamic lung volumes and transfer factor for carbon monoxide. Values of blood flow measured by a rebreathing method correlated reasonably closely with height, weight, body surface area, and lung volumes, and to a lesser extent with hand and foot size. The mean (SD) effective pulmonary blood flow index was 2.7 (0.31) 1 min-1 m-2. Small children found a single breath method of measuring flow more difficult to perform and the results were more variable. PMID:3238641

  19. Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

    PubMed Central

    Schulze-Neick, I; Penny, D; Derrick, G; Dhillon, R; Rigby, M; Kelleher, A; Bush, A; Redington, A

    2000-01-01

    BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.
OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.
DESIGN—Prospective, cross sectional study.
SETTING—Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation.
INTERVENTIONS—Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis.
MAIN OUTCOME MEASURES—Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs).
RESULTS—28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H2O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H2O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H2O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold.
CONCLUSIONS—Acute changes in pulmonary blood flow are associated

  20. Does pulmonary rehabilitation reduce peripheral blood pressure in patients with chronic obstructive pulmonary disease?

    PubMed

    Canavan, Jane L; Kaliaraju, Djeya; Nolan, Claire M; Clark, Amy L; Jones, Sarah E; Kon, Samantha S C; Polkey, Michael I; Man, William D-C

    2015-08-01

    Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50-60) m, p < 0.001) and HOME group (30 (17-42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely.

  1. Pulmonary complications of transfused blood components.

    PubMed

    Benson, Alexander B

    2012-09-01

    Three transfusion complications are responsible for the majority of the morbidity and mortality in hospitalized patients. This article discusses the respiratory complications associated with these pathophysiologic processes, including definitions, diagnosis, mechanism, incidence, risk factors, clinical management, and strategies for prevention. It also explores how different patient populations and different blood components differentially affect the risk of these deadly transfusion complications. Lastly, the article discusses how health care providers can risk stratify individual patients or patient populations to determine whether a given transfusion is more likely to benefit or harm the patient based on the transfusion indication, risk, and expected result.

  2. Pulmonary emboli from blood-biomaterial interaction

    SciTech Connect

    Coleman, J.E.; Ramberg, K.; McEnroe, C.S.; Connolly, R.J.; Callow, A.D.

    1988-07-01

    The problem of surface thrombosis and subsequent embolization remains entrenched as a yet incompletely surmounted barrier to the development of truly satisfactory intravascular prosthetic devices. A baboon ex vivo shunt was used to determine the interaction of Indium-111 platelets and potential biomaterials. The uptake of Indium-111 platelets was monitored continuously by gamma camera scanning. Several of the materials tested demonstrated a saw-toothed pattern of platelet activity, with accumulation followed by rapid decline. Neither PTFE nor Dacron exhibited this pattern. Post shunt scans of the animals' chests showed discrete foci of platelet activity in the lungs, corresponding to each embolic event noted on the material's scan. In conclusion, the search for a smooth surface as a blood material interface may produce a material which accumulates and then sloughs significant platelet aggregates. It is crucial that these materials be subjected to vigorous testing to determine their safety prior to initiation of clinical trials.

  3. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

    PubMed Central

    Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

    2016-01-01

    BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR

  4. [PULMONARY COMPLICATIONS IN CHILDREN, OPERATED ON FOR INBORN HEART FAILURES IN THE ARTIFICIAL BLOOD CIRCULATION ENVIRONMENT].

    PubMed

    Moshkivska, L V; Nastenko, E A; Golovenko, O S; Lazoryshynets, V V

    2015-11-01

    The risk factors of pulmonary complications occurrence were analyzed in children, operated on for inborn heart failures in atrificial blood circulation environment. Pulmonary complications rate and the risk factors of their occurrence were analyzed.

  5. Peculiarities of Blood Flow Changes in Venae Cavae during Experimental Pulmonary Embolism.

    PubMed

    Evlakhov, V I; Poyassov, I Z; Shaidakov, E V

    2016-10-01

    The model of acute pulmonary embolism in rabbits demonstrated reduced pulmonary blood flow, cardiac output, left atrial pressure, and blood flow in venae cavae against the background of elevated left pulmonary artery pressure and increased pulmonary vascular resistance. Simultaneously, the blood flow in the superior vena cava decreased to a lesser extent than that in the inferior vena cava, which was a characteristic feature of the model of pulmonary pathology. In contrast, when histamine was infused into the left jugular vein to equally elevate pressure in pulmonary artery as in the above model, the blood flow in the superior vena cava decreased to a greater extent than that in inferior vena cava. During stenosis of inferior vena cava that decreased the cardiac output to the level observed during modeled pulmonary embolism, the blood flows in both venae cavae dropped equally.

  6. Biodegradable radiopaque microspheres for the evaluation of regional pulmonary blood flow distribution using electron-beam computed tomography

    NASA Astrophysics Data System (ADS)

    Workman, Michael J.; Tajik, Jehangir K.; Robinson, Miguel T.; Hoffman, Eric A.

    1994-05-01

    Accurate measurement of regional pulmonary blood flow distribution is of interest both as a research and diagnostic tool. Measurements of regional pulmonary perfusion via x-ray CT offer the possibility of detecting perfusion deficits due to pulmonary embolus while maintaining a high degree of anatomic detail. Use of bolus injection of conventional radiopaque contrast with associated short mean transit times (5 - 7 seconds), requires a high degree of temporal resolution offered clinically only by electron beam x-ray CT (Imatron). The present study was intended to characterize biodegradable radiopaque microspheres as an alternative contrast agent which would allow for measurement of regional pulmonary blood flow with scanning times associated with conventional or spiral thin slice, volumetric x-ray CT protocols. To test this, a dog was scanned at 6 slice levels and 13 time points with image acquisition gated to the cardiac cycle. Lung volumes were maintained at functional residual capacity.

  7. Local pulmonary blood flow: control and gas exchange.

    PubMed

    Sheehan, D W; Farhi, L E

    1993-10-01

    We studied the local response of the pulmonary vasculature to combined changes in alveolar PO2 and PCO2 in the right apical lobe (RAL) of six conscious sheep. That lobe inspired an O2-CO2-N2 mixture adjusted to produce one of 12 alveolar gas compositions: end-tidal PCO2 (PETCO2) of 40, 50, and 60 Torr, each coupled with end-tidal PO2 (PETO2) of 100, 75, 50, and 25 Torr. In addition, at each of the four PETO2, the inspired CO2 was set to 0 and PETCO2 was allowed to vary as RAL perfusion changed. The remainder of the lung, which served as control (CL) inspired air. Fraction of the total pulmonary blood flow going to the RAL (%QRAL) was obtained by comparing the methane elimination from the RAL to that of the whole lung, and expressed as a percentage of that fraction at PETCO2 = 40, PETO2 = 100. Cardiac output, pulmonary vascular pressures, and CL gas tensions were unaffected or only minimally affected by changes in RAL gas composition. A drop in PO2 from 100 to 50 Torr decreased local blood flow by 60% in normocapnia and by 66% at a PCO2 of 60. At all levels of oxygenation, an increase in PCO2 from 40 to 60 reduced QRAL by nearly 50%. With these stimulus-response data, we developed a model of gas exchange, which takes into account the effects of test segment size on blood flow diversion. This model predicts that: (1) when the ventilation to one compartment of a two compartment lung is progressively decreased, PAO2 remains above 60 Torr for up to 60% reductions in alveolar ventilation, irrespective of compartment size; (2) the decrease in PAO2 that occurs at altitude is accompanied by a drop in PACO2 that limits the decrease in conductance and minimizes the pulmonary hypertension; and (3) as we stand, local blood flow control by the alveolar gas tensions halves the alveolar-arterial PO2 and PCO2 differences imposed by gravity.

  8. [Fetal pulmonary artery blood flow depending on fetal lung maturity].

    PubMed

    Jastrzebski, Arkadiusz; Lech, Tomasz; Obcowska-Lech, Marta; Sobański, Andrzej; Sipiński, Adam

    2004-01-01

    The ultrasonographic assessment of fetal lung maturity by evaluating the elasticity of lung tissue, Dynamic Lung Score (DLS) has been being performed since 1986 in ObGyn Department in Tychy (Medical University of Silesia). The lung elasticity is evaluated on the cross sections of fetal thorax, on the level of heart ventricles. The result of the evaluation is given as the three degree scale, in which I degree indicates the lack of elasticity and fetal lung immaturity, II degrees indicates partially expressed elasticity, corresponding with incomplete maturity of lung tissue, and III degrees represents full elasticity and indicates complete maturity of fetal lungs. This study was designed to compare fetal pulmonary artery blood flow with the maturity of fetal lung tissue evaluated during the ultrasonographic assessment of fetal lung tissue elasticity. The examination was performed on pregnant women, beginning on 27th week gestation. During the examination the mean Pulsatility Index was decreased, particularly in fetuses with II degrees lung maturity. The Resistance Index (RI) was found to be stable and independent of gestational age. In the group with I degree lung maturity (DLS I), the mean PI = 2.643 (+/- 0.229), mean RI = 0.879 (+/- 0.036), in DLS II group PI = 2.039 (+/- 0.262), RI = 0.868 (+/- 0.037), and in DLS III group PI = 2,500 (+/- 0.100), RI = 0.900 (+/- 0.100). Comparing the ultrasonographic evaluation of fetal lung maturity with fetal pulmonary artery blood flow allows more accurate assessment of fetal lung maturity. Fetal lung maturity can not be evaluated univocally on the basis of blood flow assessment. Because of the divergence of blood flow parameters further studies including bigger population seem to be necessary for verification of the results and for establishing the reference values.

  9. Caring for patients with lesions increasing pulmonary blood flow.

    PubMed

    Moynihan, P J; King, R

    1989-06-01

    The most common congenital cardiac defect is VSD. This malady accounts for 20 to 30 per cent of all congenital cardiac defects and is representative of a cardiac lesion that increases pulmonary blood flow. Although lesions, which increase pulmonary blood flow, may vary in incidence, they frequently have common symptomatology. Over time, congestive heart failure becomes a problem. Poor respiratory status leads to weight loss, poor feeding, and failure to thrive. If unrepaired, the child often presents with cyanosis and tachypnea. The history may include frequent respiratory infections, exercise intolerance, generalized malaise, or fatigue. In spite of poor weight gain, the child may be edematous and have a large liver. Definitive diagnosis of each lesion may be made by echocardiogram, cardiac catheterization, or both. With these data and a detailed history, treatment and management decisions are determined. In most cases, as the child gets older, symptoms become more evident. This is the result of high pulmonary pressure. High pressure over time causes a thickening of the alveolar tissue, which decreases the permeability of the alveolar membranes for gas exchange. Lung changes can become irreversible, but it is unusual for irreversible changes to occur before 1 year of age. All the lesions described in this article are amendable to primary repair before 1 year of age, affording the best functional results. Postoperative nursing care includes management of persisting CHF and PVR while maintaining adequate cardiac output. Many factors, including electrolyte balance, nutritional status, conduction disturbances, stress, and parental anxiety, influence the management of these infants. The outcome depends greatly on the assessment skill of a highly competent cardiac intensive care nurse and an environment conducive to collaborative practice.

  10. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  11. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  12. Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

    PubMed

    Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

    2005-11-01

    Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

  13. How the python heart separates pulmonary and systemic blood pressures and blood flows.

    PubMed

    Jensen, Bjarke; Nielsen, Jan M; Axelsson, Michael; Pedersen, Michael; Löfman, Carl; Wang, Tobias

    2010-05-01

    The multiple convergent evolution of high systemic blood pressure among terrestrial vertebrates has always been accompanied by lowered pulmonary pressure. In mammals, birds and crocodilians, this cardiac separation of pressures relies on the complete division of the right and left ventricles by a complete ventricular septum. However, the anatomy of the ventricle of most reptiles does not allow for complete anatomical division, but the hearts of pythons and varanid lizards can produce high systemic blood pressure while keeping the pulmonary blood pressure low. It is also known that these two groups of reptiles are characterised by low magnitudes of cardiac shunts. Little, however, is known about the mechanisms that allow for this pressure separation. Here we provide a description of cardiac structures and intracardiac events that have been revealed by ultrasonic measurements and angioscopy. Echocardiography revealed that the atrioventricular valves descend deep into the ventricle during ventricular filling and thereby greatly reduce the communication between the systemic (cavum arteriosum) and pulmonary (cavum pulmonale) ventricular chambers during diastole. Angioscopy and echocardiography showed how the two incomplete septa, the muscular ridge and the bulbuslamelle - ventricular structures common to all squamates - contract against each other in systole and provide functional division of the anatomically subdivided ventricle. Washout shunts are inevitable in the subdivided snake ventricle, but we show that the site of shunting, the cavum venosum, is very small throughout the cardiac cycle. It is concluded that the python ventricle is incapable of the pronounced and variable shunts of other snakes, because of its architecture and valvular mechanics.

  14. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.

    PubMed

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.

  15. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

    PubMed Central

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701

  16. Pulmonary blood volume (PRV) in rats with chronic mountain sickness

    SciTech Connect

    Ou, L.C.; Sardella, G.L.; Hill, N.S.; Tenney, S.M.

    1986-03-05

    Upon chronic exposure to severe hypoxia, Hilltop (H) strain of Sprague-Dawley rats develops excessive polycythemia, severe hypervolemia and marked elevation in pulmonary arterial pressure (PAP), whereas Madison (M) strain develops only moderate responses. Hypervolemia is expected to increase the PBV which might contribute to the development of severe pulmonary hypertension. Two groups of 6 animals each of the H and M strains were exposed to sea level (SL) and a simulated altitude of 18,000 ft for 14 days. At the end of exposure each animal was measured for RBC volume (RBCV), total blood volume (TBV), PBV and PAP under normoxia for control and under hypoxia (10% O/sub 2/) for the hypoxic groups. RBCV was determined by /sup 51/Cr-RBC dilution and PBV was trapped by tightening an implanted loose ligature around the ascending aorta and PA. There were not strain differences in all parameters studied at SL. RBCV, TBV and PAP increased with hypoxia in both strains but significantly more so in H than M. PBV per g lung WT decreased in both strains despite elevated TBV and PAP, but more so in M than H. There were good correlations between the PBV and TBV, and between PAP and PBV in the hypoxic H and M rats. The data suggest that chronic hypoxia reduced the distensibility and perhaps the vascular capacity of the lungs such that small relative increase in PBV could significantly contribute to the rise in PAP.

  17. Expression of peptide fragments from proADM and involvement of mitogen-activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow.

    PubMed

    Li, Wei; Guo, Aili; Wang, Lijuan; Kong, Qingyu; Wang, Rong; Han, Li; Zhao, Cuifen

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N-terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal-regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly higher ADT was lower, and p-p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p-ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow.

  18. Pulmonary blood flow redistribution by increased gravitational force

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Chornuk, M. A.; Self, D. A.; Kallas, H. J.; Burns, J. W.; Bernard, S.; Polissar, N. L.; Glenny, R. W.

    1998-01-01

    This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

  19. Pulmonary blood flow redistribution by increased gravitational force

    NASA Technical Reports Server (NTRS)

    Hlastala, M. P.; Chornuk, M. A.; Self, D. A.; Kallas, H. J.; Burns, J. W.; Bernard, S.; Polissar, N. L.; Glenny, R. W.

    1998-01-01

    This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

  20. Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

    PubMed

    Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

    2015-09-01

    Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

  1. Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

    PubMed Central

    Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

    2015-01-01

    Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

  2. Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation.

    PubMed

    West, John B

    2013-02-01

    In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

  3. Effect of Pulmonary Blood Flow upon Lung Mechanics*

    PubMed Central

    Giannelli, Stanley; Ayres, Stephen M.; Buehler, M. E.

    1967-01-01

    Airway pressure was continuously recorded in an isolated horizontally mounted canine heart-lung preparation during abrupt, stepwise 100-200 ml inflations to 20-25 cm water pressure, and subsequent deflations. With each change in volume there was a steep rise or fall in pressure, followed by stress relaxation to a static equilibrium airway pressure. Comparison was made between the nonperfused state and during perfusion with whole blood at 100 ml/kg dog wt per min, and left atrial pressure of 10 mm Hg. Pressure tracings were similar during deflation in the perfused and the nonperfused lung. During inflation, in the middle range of lung inflation volumes, the peak inflation and equilibrium airway pressures were greater in the nonperfused state; maximum difference of static pressures in nine preparations averaged 146% of perfused values and the average stress relaxation difference from eight of these was 276%. Lung distensibility was the same with packed red cells or plasma perfusates and was not changed by varying the perfusion rate up to 220 ml/kg per min. During cyclic ventilation, dynamic compliance was similarly greater in the perfused than in the nonperfused state in the middle range of inflation volumes. Static distention of the vascular bed produced similar results with progressive improvement in distensibility in mid-inflation range up to a hydrostatic pressure of 15 cm blood. These data suggest that the distended pulmonary vascular bed provides structural airway support which facilitates entry of gas into the terminal respiratory units at diminished pressure. PMID:6061740

  4. Blood gas analysis in dogs with pulmonary heartworm disease.

    PubMed

    Kitagawa, H; Yasuda, K; Sasaki, Y

    1993-04-01

    Blood gases were analyzed in dogs with pulmonary heartworm (HW) disease. The arterial oxygen tension (PaO2) in dogs with mild signs of dirofilariasis (mildly affected group, n = 48, 85.7 +/- 8.2 mmHg) and in dogs with signs of right heart failure (severely affected group, n = 13, 76.4 +/- 11.6 mmHg) was lower (p < 0.01) than in dogs without HW infection (HW-free group, n = 19, 91.5 +/- 7.3 mmHg). Only 2 dogs in the severely affected group had a PaO2 less than 60 mmHg. The arterial carbon dioxide tension (PaCO2, p < 0.01) and mixed venous O2 (p < 0.01) and CO2 (p < 0.01) tensions were lower, and alveolar-arterial oxygen difference (AaDO2, p < 0.01) was greater in the severely affected group than in the HW-free and mildly affected groups. Arterial pH and bicarbonate (HCO3-) concentrations were lower (p < 0.01) in both affected groups than in the HW-free groups. The anion gap level was not different among the 3 groups. Serum lactic acid level in the severely affected group was higher (p < 0.01) than in the HW-free and mildly affected groups. However, a slightly higher serum lactic acid concentration was found only in 2 dogs of the severely affected group (3.84 mmol/l and 3.82 mmol/l). The PaO2 (r = -0.62) and AaDO2 (r = 0.66) correlated significantly (p < 0.01) with mean pulmonary arterial pressure. One week after HW removal, blood gases, pH and HCO3- concentration remained unchanged in the mildly affected group. In the severely affected group, blood gas values were the same, but pH and HCO3- concentration improved slightly.

  5. Pulmonary Manifestations of the Pre-Engraftment Syndrome after Umbilical Cord Blood Transplantation

    PubMed Central

    Brownback, Kyle R.; Simpson, Steven Q.; McGuirk, Joseph P.; Lin, Tara L.; Abhyankar, Sunil; Ganguly, Siddhartha; Aljitawi, Omar S.

    2014-01-01

    Pre-engraftment syndrome (PES) is a condition occurring after umbilical cord blood transplantation (UCBT) characterized by fever and erythematous skin rash prior to neutrophil engraftment. We sought to determine the incidence and characterize the pulmonary manifestations of PES. A retrospective review of patients who underwent UCBT at the University of Kansas Medical Center over a 5 year period was performed. Data collected included patient baseline characteristics, presence of PES, pulmonary findings, treatments and survival. Forty-four patients underwent UCBT with 22 of those patients developing PES. Full-intensity myeloablative conditioning regimen was found to be a risk factor for development of PES. Of those 22 patients, 13 had resting hypoxemia. The most common radiographic findings included diffuse ground glass opacities with pleural effusions. Fifteen patients with PES received corticosteroids, of which twelve had improvement in fevers and rash. These patients had a trend towards worse mortality than those not receiving corticosteroids. There was a non-significant trend towards worse survival in patients with PES and hypoxemia compared to those without hypoxemia. PES is a common complication following cord blood transplantation, with hypoxemia being present in over half of patients with PES. Hypoxemia with PES and treatment with corticosteroids may portend a worse prognosis. PMID:24346710

  6. Altered Immune Phenotype in Peripheral Blood Cells of Patients with Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Risbano, Michael G; Meadows, Christina A; Coldren, Christopher D; Jenkins, Tiffany J.; Edwards, Michael G; Collier, David; Huber, Wendy; Mack, Douglas G; Fontenot, Andrew P; Geraci, Mark W; Bull, Todd M

    2010-01-01

    Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease. Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T-cells from scleroderma patients with pulmonary hypertension. Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations for early diagnosis and provide insight into mechanisms of scleroderma-related pulmonary hypertension. PMID:20973920

  7. Blood gas analysis, blood saturation and chosen parameters of spirometric examination in NSCLC patients undergoing chemotherapy and pulmonary rehabilitation.

    PubMed

    Tokarski, Sławomir; Tokarska, Kamila; Schwarz, Ewa; Obrebska, Agnieszka; Mejer, Anna; Kowalski, Jan

    2014-04-01

    In industrialized countries lung cancer is associated with highest mortality among carcinoma. Progression of the disease is associated with diminished tolerance for physical activities, aggravated dyspnea and lowering of life quality. The aim of study was the evaluation of blood gas, blood saturation and chosen parameters of spirometric examination in NSCLC patients undergoing chemotherapy and pulmonary rehabilitation. Analysis of capillary blood was done using RapidPoint 405 Siemens device. Spirometric examination was done using PNEUMO abcMED device. Forty-nine patients with inoperable NSCLC were subjected to the examination. This included 38 men and 11 women aged between 46-75 years (mean age 63 +/- 7.5 years) who were separated into two groups: group I--25 patients undergoing standard chemotherapy (group C); group II--24 patients undergoing standard chemotherapy and pulmonary rehabilitation (group CK). All patients were subjected to blood gas analysis, blood saturation analysis and spirometric examination twice, before and after first-line chemotherapy Increase of pO2 and SaO2 in blood, and FEV1 and FVC in spirometric examination was significantly higher in patients undergoing pulmonary rehabilitation and chemotherapy (group II) (p < 0.05) in comparison to NSCLC patients undergoing only chemotherapy (group I). Pulmonary rehabilitation of NSCLC patients undergoing first-line chemotherapy results in improvement of indicators of blood gas, blood saturation analysis and chosen parameters of spirometric analysis. Pulmonary rehabilitation in patients with lung cancer seems to be an important form of supplementary treatment.

  8. Problems in cerebral blood flow calculation using xenon-133 in patients with pulmonary diseases

    SciTech Connect

    Hansen, M.; Jakobsen, M.; Enevoldsen, E.; Egede, F. )

    1990-05-01

    We used the end-tidal concentration of xenon-133 (air curve) to estimate the profile of its arterial concentration in calculating cerebral blood flow. We examined the effects of pulmonary disease and artificial ventilation on the air curve and the calculated cerebral blood flow. We studied the relation between arterial and end-tidal xenon activities in 19 subjects, of whom 15 had pulmonary dysfunction. The t 1/2 of the declining phases of the arterial and air curves were used to express their shapes. The mean +/- SD reference t 1/2 from 15 normal volunteers was 26.8 +/- 8.4 seconds. The mean +/- SD t 1/2 s of the air and arterial curves from the 15 patients with pulmonary dysfunction were 10.4 +/- 2.9 and 33.8 +/- 10.9 seconds. The degree of pulmonary dysfunction (expressed as the pulmonary shunt percentage) correlated with distortion of the air curve. Substituting the arterial for the air curve, mean calculated cerebral blood flow (as the initial slope index) increased from 40 to 61 for the 12 patients with chronic obstructive pulmonary disease. The degree of underestimation of cerebral blood flow using the air curve correlated with the pulmonary shunt percentage. Our work confirms the problems of estimating cerebral blood flow in subjects with pulmonary dysfunction.

  9. Pulmonary and systemic blood flow contributions to upper airways in canine lung

    SciTech Connect

    Barman, S.A.; Ardell, J.L.; Parker, J.C.; Perry, M.L.; Taylor, A.E. )

    1988-11-01

    The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-{mu}m radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly higher, and higher in the upper segments. The pulmonary and systemic circulations each contributed {approximately}50% to the main bronchi blood flow. The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute {approximately}50% of the blood flow to the main bronchi in dog lungs.

  10. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

  11. Measurement of pulmonary capillary blood flow in infants by plethysmography.

    PubMed

    Stocks, J; Costeloe, K; Winlove, C P; Godfrey, S

    1977-03-01

    An accurate method for measuring effective pulmonary capillary blood flow (Qc eff) in infants has been developed with an adaptation of the plethysmographic technique. Measurements were made on 19 preterm. 14 small-for-dates, and 7 fullterm normal infants with a constant volume whole body plethysmograph in which the infant rebreathed nitrous oxide. There was a highly significant correlation between Qc eff and body weight, and this relationship was unaffected by premature delivery or intrauterine growth retardation. Mean Qc eff in preterm, small-for dates, and fullterm infants was 203, 208 and 197 ml min-1 kg-1, respectively, with no significant differences between the groups. A significant negative correlation existed between Qc eff and haematocrit in the preterm infants. There was no relationship between weight standardized Qc eff and postnatal age in any of the groups. With this technique, it was possible to readily recognise the presence of rapid recirculation (indicative of shunting) in several of the infants, suggesting that rebreathing methods for the assessment of Qc eff should not be applied indiscriminately during the neonatal period. By taking care to overcome the potential sources of technical error, it was possible to obtain highly reproducible results of Qc eff in infants over a wider age range than has been previously reported.

  12. Abnormal distribution of pulmonary blood flow in aortic valve disease. Relation between pulmonary function and chest radiograph.

    PubMed

    Goodenday, L S; Simon, G; Craig, H; Dalby, L

    1970-05-01

    Wasted ventilatory volume (V(D)) and its ratio to tidal volume (V(D)/V(T)) were measured at rest and during exertion in 17 patients with aortic valve disease. We considered V(D)/V(T) to indicate abnormal ventilation: perfusion relations if it did not decrease on exertion, or if the exercising value was greater than 40 per cent. Plain chest radiographs were independently examined for evidence of diversion of pulmonary blood to the upper lobes. There was significant agreement (p<0.05) between radiographic and pulmonary function estimations of abnormality. This suggests that the raised pulmonary venous pressure associated with left ventricular failure creates an abnormal pattern of blood flow through the lung, which is responsible for causing inadequate perfusion with respect to ventilation.

  13. Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery?

    PubMed Central

    Chowdhury, Ujjwal Kumar; Kapoor, Poonam Malhotra; Rao, Keerthi; Gharde, Parag; Kumawat, Mukesh; Jagia, Priya

    2016-01-01

    We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID:27397472

  14. Blood cell characterization by light scattering

    NASA Astrophysics Data System (ADS)

    Magnin, Olivier

    2004-09-01

    In this paper we are going to introduce optical methods for blood cell characterization performed by standard hematology analyzers. As a consequence, we are going to focus on methods that are, or will be, compatible with an average cost, commercial, blood cell counter.

  15. Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects.

    PubMed

    Cheng, Andrew L; Takao, Cheryl M; Wenby, Rosalinda B; Meiselman, Herbert J; Wood, John C; Detterich, Jon A

    2016-04-01

    After the Fontan procedure, patients with univentricular hearts can experience long-term complications due to chronic low-shear non-pulsatile pulmonary blood flow. We sought to evaluate hemorheology and its relationship to hemodynamics in children with univentricular hearts. We hypothesized that low-shear blood viscosity and red blood cell (RBC) aggregation would be associated with increased pulmonary vascular resistance (PVR) and decreased pulmonary blood flow (PBF). We performed a cross-sectional analysis of 62 children undergoing cardiac catheterization-20 with isolated atrial septal defect (ASD), 22 status post Glenn procedure (Glenn), and 20 status post Fontan procedure (Fontan). Shear-dependent blood viscosity, RBC aggregation and deformability, complete blood count, coagulation panel, metabolic panel, fibrinogen, and erythrocyte sedimentation rate were measured. PVR and PBF were calculated using the Fick equation. Group differences were analyzed by ANOVA and correlations by linear regression. Blood viscosity at all shear rates was higher in Glenn and Fontan, partially due to normocytic anemia in ASD. RBC aggregation and deformability were similar between all groups. Low-shear viscosity negatively correlated with PBF in Glenn and Fontan only (R (2) = 0.27, p < 0.001); it also negatively correlated with pulmonary artery pressure in Glenn (R (2) = 0.15, p = 0.01), and positively correlated with PVR in Fontan (R (2) = 0.28, p = 0.02). Our data demonstrate that elevated low-shear blood viscosity is associated with negative hemodynamic perturbations in a passive univentricular pulmonary circulation, but not in a pulsatile biventricular pulmonary circulation.

  16. The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

    PubMed

    Ghimire, Anukul; Andersen, Mads J; Burrowes, Lindsay M; Bouwmeester, J Christopher; Grant, Andrew D; Belenkie, Israel; Fine, Nowell M; Borlaug, Barry A; Tyberg, John V

    2016-12-01

    Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies. Copyright © 2016 the American Physiological Society.

  17. [Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique].

    PubMed

    Gamroth, A H; Schad, L R; Wacker, C M; Gehling, U; Knopp, M V; Betsch, B; Clorius, J H; van Kaick, G

    1992-04-01

    MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.

  18. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow.

    PubMed

    Ghorishi, Zahra; Milstein, Jay M; Poulain, Francis R; Moon-Grady, Anita; Tacy, Theresa; Bennett, Stephen H; Fineman, Jeffery R; Eldridge, Marlowe W

    2007-06-01

    Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

  19. Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network.

    PubMed

    Seo, Hyejin; Kim, Jinsun; Park, Gi-Hee; Kim, Yuri; Cho, Sung-Won

    2016-09-01

    Intimate crosstalk occurs between the pulmonary epithelium and the vascular network during lung development. The transcription factor forkhead box f1 (Foxf1) is expressed in the lung mesenchyme and plays an indispensable role in pulmonary angiogenesis. Sonic hedgehog (Shh), a signalling molecule, is expressed in lung epithelium and is required to establish proper angiogenesis. It has been suggested that Foxf1, a downstream target of the Shh signalling pathway, mediates interaction between angiogenesis and the epithelium in lung. However, there has been no clear evidence showing the mechanism how Foxf1 is regulated by Shh signalling pathway during lung development. In this study, we investigated the lung-specific enhancers of Foxf1 and the Gli binding on the enhancers. At first, we found three evolutionarily conserved Foxf1 enhancers, two of which were long-range enhancers. Of the long-range enhancers, one demonstrated tissue-specific activity in the proximal and distal pulmonary blood vessels, while the other one demonstrated activity only in distal blood vessels. At analogous positions in human, these long-range enhancers were included in a regulatory region that was reportedly repeatedly deleted in alveolar capillary dysplasia with misalignment of pulmonary vein patients, which indicates the importance of these enhancers in pulmonary blood vessel formation. We also determined that Gli increased the activity of one of these long-range enhancers, which was specific to distal blood vessel, suggesting that Shh regulates Foxf1 transcription in pulmonary distal blood vessel formation.

  20. Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

    1997-01-01

    BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

  1. Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

    1997-01-01

    BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

  2. Simultaneous Pulmonary and Systemic Blood Pressure and ECG Interval Measurement in Conscious, Freely Moving Rats

    PubMed Central

    Rey, Markus; Weber, Edgar W; Hess, Patrick D

    2012-01-01

    Here we evaluated the ability of a new, dual blood-pressure telemetry transmitter to simultaneously measure pulmonary and systemic blood pressure and the electrocardiogram in rats. The transmitter was implanted in normotensive and monocrotaline-induced pulmonary hypertensive Wistar rats, with sensing catheters placed in the pulmonary artery (channel 1) and descending aorta (channel 2). Biopotential electrodes were positioned to record an apex-based lead II electrocardiogram. Pulmonary and systemic arterial blood pressure and electrocardiographic waveforms were recorded between 2 and 12 wk after implantation of the transmitter. During this period, pulmonary arterial pressure progressively increased in monocrotaline-treated compared with saline-treated rats. The pharmacologic response of rats to reference compounds was measured by using the transmitter to validate the technique and to evaluate the ability of the device to transmit changes in blood pressure and the electrocardiogram. Validation against 2 Millar high-fidelity blood-pressure catheters confirmed the accuracy of the blood pressure data recorded with the transmitter. In addition, local tolerance of the associated catheters was confirmed by histologic examination. PMID:22776124

  3. Simultaneous pulmonary and systemic blood pressure and ECG Interval measurement in conscious, freely moving rats.

    PubMed

    Rey, Markus; Weber, Edgar W; Hess, Patrick D

    2012-03-01

    Here we evaluated the ability of a new, dual blood-pressure telemetry transmitter to simultaneously measure pulmonary and systemic blood pressure and the electrocardiogram in rats. The transmitter was implanted in normotensive and monocrotaline-induced pulmonary hypertensive Wistar rats, with sensing catheters placed in the pulmonary artery (channel 1) and descending aorta (channel 2). Biopotential electrodes were positioned to record an apex-based lead II electrocardiogram. Pulmonary and systemic arterial blood pressure and electrocardiographic waveforms were recorded between 2 and 12 wk after implantation of the transmitter. During this period, pulmonary arterial pressure progressively increased in monocrotaline-treated compared with saline-treated rats. The pharmacologic response of rats to reference compounds was measured by using the transmitter to validate the technique and to evaluate the ability of the device to transmit changes in blood pressure and the electrocardiogram. Validation against 2 Millar high-fidelity blood-pressure catheters confirmed the accuracy of the blood pressure data recorded with the transmitter. In addition, local tolerance of the associated catheters was confirmed by histologic examination.

  4. Doppler echocardiographic evaluation of pulmonary blood flow after the Fontan operation: the role of the lungs.

    PubMed Central

    Penny, D J; Redington, A N

    1991-01-01

    OBJECTIVE--To document whether the act of respiration influences pulmonary blood flow in patients after the Fontan operation. DESIGN--Prospective study in which patients acted as their own controls. SETTING--Supraregional paediatric cardiology centre. PATIENTS--Sixteen patients who had undergone atriopulmonary anastomosis (Fontan operation) for the treatment of congenital heart disease. INTERVENTION--Doppler assessment of pulmonary artery flow patterns with a simultaneous respirometer, electrocardiogram and phonocardiogram. RESULTS--Total (mean (1SD) ) forward pulmonary flow was 63.6 (35)% higher during inspiratory cardiac cycles than during expiratory ones. CONCLUSIONS--The act of breathing provides an additional energy supply to pulmonary blood flow in patients after the Fontan operation. Images PMID:1747298

  5. Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

    PubMed

    Henderson, A Cortney; Levin, David L; Hopkins, Susan R; Olfert, I Mark; Buxton, Richard B; Prisk, G Kim

    2006-08-01

    Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.

  6. Gravitational effects on the distribution of pulmonary blood flow: hemodynamic misconceptions.

    PubMed

    Badeer, H S

    1982-01-01

    In the upright individual the apex of the lung receives relatively little blood. This has often been explained by the low pulmonary arterial pressure which is said to be just sufficient to raise the blood to the apex. It is believed that pulmonary arterial pressure must overcome the pressure due to gravity. This misconception overlooks the fact that the siphon principle applies to the vascular system in which the gravitational pressure of venous blood counterbalances the gravitational pressure of blood in the arteries and vice versa. Accordingly, the perfusion or driving pressure (P1-P2) between arteries and veins at any horizontal level of the lung remains unchanged, irrespective of body position. Intravascular pressure at any point is the algebraic sum of dynamic pressure causing flow (cardiogenic) and the pressure of blood due to gravity which does not cause flow. In the upright position, since the dynamic pressure in the pulmonary circuit is low, the drop in gravitational pressure at the apex of the lung reduces significantly the intravascular and, consequently, the transmural pressure in these vessels. The pulmonary microvessels being highly compliant undergo collapse and increase their resistance to flow. The reduction in apical flow is, therefore, a consequence of increased vascular resistance and not a matter of raising the blood against gravity. Gravitational pressure of blood per se neither hinders upward flow nor favors downward flow.

  7. Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation

    PubMed Central

    Blood, Arlin B.; Schroeder, Hobe J.; Terry, Michael H.; Merrill-Henry, Jeanette; Bragg, Shannon L.; Vrancken, Kurt; Liu, Taiming; Herring, Jason L.; Sowers, Lawrence C.; Wilson, Sean M.; Power, Gordon G.

    2011-01-01

    Background Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO. Methods and Results Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 M), or an intravascular nitrite infusion (3 mg·hr−1 bolus, 5 mg·kg−1·hr−1 infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed while breathing the nitrite aerosol (~20 ppb NO) but not during intravascular infusion of nitrite. Conclusions We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application. PMID:21282501

  8. [Effects of air pollution on pulmonary blood vessels].

    PubMed

    Zaiats, L M

    1995-01-01

    The experiments on white rats provided histological and electron-microscopic evidence on the damage which may be done to pulmonary vessels by the chemicals present in polluted atmospheric air. There appeared impairment of vascular permeability and perivascular edema late in the experiment course (within 3 months). Alveolar capillaries proved most sensitive to air pollution.

  9. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    PubMed

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  10. Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

    PubMed

    Grossherr, M; Hengstenberg, A; Dibbelt, L; Igl, B-W; Noel, R; Knesebeck, A v d; Schmucker, P; Gehring, H

    2009-10-01

    The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646,000 for goats and between 17,000 and 267,000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between -106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

  11. Pulmonary Vascular Impedance in Chronic Pulmonary Hypertension.

    DTIC Science & Technology

    PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA, PHYSIOLOGY.

  12. Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI

    NASA Astrophysics Data System (ADS)

    Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger

    2015-03-01

    In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.

  13. Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow

    NASA Technical Reports Server (NTRS)

    Chevalier, P. A.; Reed, J. H., Jr.; Vandenberg, R. A.; Wood, E. H.

    1978-01-01

    Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic 'balance point' for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.

  14. Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow

    NASA Technical Reports Server (NTRS)

    Chevalier, P. A.; Reed, J. H., Jr.; Vandenberg, R. A.; Wood, E. H.

    1978-01-01

    Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic 'balance point' for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.

  15. Characterization of red blood cell deformability change during blood storage.

    PubMed

    Zheng, Yi; Chen, Jun; Cui, Tony; Shehata, Nadine; Wang, Chen; Sun, Yu

    2014-02-07

    Stored red blood cells (RBCs) show progressive deformability changes during blood banking/storage. Their deformability changes over an 8 weeks' storage period were measured using a microfluidic device. Hydrodynamic focusing controls the orientation and position of individual RBCs within the microchannel. High-speed imaging (5000 frames s(-1)) captures the dynamic deformation behavior of the cells, and together with automated image analysis, enables the characterization of over 1000 RBCs within 3 minutes. Multiple parameters including deformation index (DI), time constant (shape recovery rate), and RBC circularity were quantified. Compared to previous studies on stored RBC deformability, our results include a significantly higher number of cells (>1000 cells per sample vs. a few to tens of cells per sample) and, for the first time, reveal deformation changes of stored RBCs when traveling through human-capillary-like microchannels. Contrary to existing knowledge, our results demonstrate that the deformation index of RBCs under folding does not change significantly over blood storage. However, significant differences exist in time constants and circularity distribution widths, which can be used to quantify stored RBC quality or age.

  16. Blood characterization using UV/vis spectroscopy

    NASA Astrophysics Data System (ADS)

    Mattley, Yvette D.; Mitrani-Gold, F.; Orton, S.; Bacon, Christina P.; Leparc, German F.; Bayona, M.; Potter, Robert L.; Garcia-Rubio, Luis H.

    1995-05-01

    The current methods used for typing blood involve an agglutination reaction which results from the association of specific antibodies with antigens present on the erythrocyte cell surface. While this method is effective, it requires involved laboratory procedures to detect the cell surface antigens. As an alternative technique, uv/vis spectroscopy has been investigated as a novel way to characterize and differentiate the blood types. Typing with this technique is based on spectral differences which appear throughout portions of both the ultraviolet and visible range. The origin of these spectral differences is unknown and presently under investigation. They may be due to intrinsic absorption differences at the molecular level, and/or they may be due to scattering differences brought about by either subtle variation in cell surface characteristics, cell shape or state of aggregation. As the background optical density in these samples is identified and accounted for, the spectral differences become more defined. This work and the continuation of this project will be included in a general database encompassing a wide range of blood samples. In addition, long term goals involve the investigation of diseased blood with the potential of providing a more rapid diagnosis for blood borne pathogens.

  17. Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth.

    PubMed

    Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; Te Pas, Arjan B; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

    2017-03-01

    Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X-ray imaging and angiography in near-term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration. Air entry into the lungs at birth triggers major cardiovascular changes, including a large increase in pulmonary blood flow (PBF) that is not spatially related to regional lung aeration. To investigate the possible underlying role of a vagally-mediated stimulus, we used simultaneous phase-contrast X-ray imaging and angiography in near-term (30 days of gestation) vagotomized (n = 15) or sham-operated (n = 15) rabbit kittens. Rabbits were imaged before ventilation, when one lung was ventilated (unilateral) with 100% nitrogen (N2 ), air or 100% oxygen (O2 ), and after all kittens were switched to unilateral ventilation in air and then ventilation of both lungs using air. Compared to control kittens, vagotomized kittens had little or no increase in PBF in both lungs following unilateral ventilation when ventilation occurred with 100% N2 or with air. However, relative PBF did increase in vagotomized animals ventilated with 100% O2 , indicating the independent stimulatory effects of local oxygen concentration and autonomic innervation on the changes in PBF at birth. These findings demonstrate that vagal denervation inhibits the previously observed increase in PBF with partial lung aeration, although high inspired oxygen concentrations can partially

  18. Automated Measurement of Microcirculatory Blood Flow Velocity in Pulmonary Metastases of Rats

    PubMed Central

    Fontanella, Andrew N.; Palmer, Gregory M.; Boico, Alina; Min, Hooney; Dewhirst, Mark W.; Irwin, David C.; Zhao, Yulin; Schroeder, Thies

    2014-01-01

    Because the lung is a major target organ of metastatic disease, animal models to study the physiology of pulmonary metastases are of great importance. However, very few methods exist to date to investigate lung metastases in a dynamic fashion at the microcirculatory level, due to the difficulty to access the lung with a microscope. Here, an intravital microscopy method is presented to functionally image and quantify the microcirculation of superficial pulmonary metastases in rats, using a closed-chest pulmonary window and automated analysis of blood flow velocity and direction. The utility of this method is demonstrated to measure increases in blood flow velocity in response to pharmacological intervention, and to image the well-known tortuous vasculature of solid tumors. This is the first demonstration of intravital microscopy on pulmonary metastases in a closed-chest model. Because of its minimized invasiveness, as well as due to its relative ease and practicality, this technology has the potential to experience widespread use in laboratories that specialize on pulmonary tumor research. PMID:25490280

  19. Pulmonary microthromboembolism by injection of sonicated autologous blood in rabbits with splenic artery ligations.

    PubMed

    Kietthubthew, S; Kisanuki, A; Asada, Y; Marutsuka, K; Funahara, Y; Sumiyoshi, A

    1997-01-01

    Chronic pulmonary thromboembolism (PTE) has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE seen in thalassemic patients after splenectomy. We divided New Zealand white rabbits into three groups: Group 1 was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we counted the platelet number until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after injection of the sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

  20. Intravenous injection of sonicated blood induces pulmonary microthromboembolism in rabbits with ligation of the splenic artery.

    PubMed

    Kisanuki, A; Kietthubthew, S; Asada, Y; Marutsuka, K; Funahara, Y; Sumiyoshi, A

    1997-01-15

    Pulmonary thromboembolism (PTE) is found in long hospitalized patients. Chronic PTE has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE. We divided New Zealand white rabbits into three groups: Group I was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we examined the platelet counts every 10 minutes until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after the injection of sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

  1. Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

    1999-01-01

    We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

  2. Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

    1999-01-01

    We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

  3. Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity

    NASA Technical Reports Server (NTRS)

    Prisk, G. K.; Guy, Harold J. B.; Elliott, Ann R.; Deutschman, Robert A., III; West, John B.

    1993-01-01

    We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to nine days of microgravity. DL in microgravity was elevated compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc and Dm. The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value. We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to eight days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased inflight and decreased postflight compared with preflight standing. Compared with preflight standing, SV was increased 46 percent inflight and decreased 14 percent in the 1st week postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

  4. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    PubMed

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study.

  5. CASE REPORT Acute Compartment Syndrome of the Forearm Following Blood Gas Analysis Postthrombolysis for Pulmonary Embolism.

    PubMed

    Bisarya, Kamal; George, Samuel; El Sallakh, Sam

    2013-01-01

    Acute compartment syndrome is an important condition with potentially serious consequences if not diagnosed and treated promptly. This report highlights a case of acute compartment syndrome of the forearm after radial artery blood gas analysis in a patient who had been thrombolyzed for a pulmonary embolus. Methods/Case Report: We present a case of a 54-year-old lady, admitted and treated for a pulmonary embolism with tenecteplase for thrombolysis. As per routine management, she had taken an arterial blood gas sample, which caused hematoma in the wrist and a few hours later developed pain and a tense right forearm being diagnosed with compartment syndrome. She underwent fasciotomies and subsequent split skin grafting. We discuss the different etiologies of compartment syndrome, clinical signs, and available investigations as well as immediate and definitive management options including fasciotomy techniques. We present the latest literature on the subject and extract valuable learning points from this case. With the common use of thrombolysis for the management of a myocardial infarction or pulmonary embolus, compartment syndrome is an uncommon but potentially associated problem. Furthermore, with blood gas sampling being part of daily clinical practice and a potential cause of this condition, the compartment syndrome becomes iatrogenic and potentiates serious litigation. As many junior doctors are performing blood gas analysis postthrombolysis, they need to assess patients adequately and realize the risk of possible sequelae such as compartment syndrome in this group and inform patients of such complications.

  6. Serum white blood cell count and pulmonary function test are negatively associated.

    PubMed

    Yang, H-F; Kao, T-W; Wang, C-C; Peng, T-C; Chang, Y-W; Chen, W-L

    2015-12-01

    A variety of inflammatory disorders influence the serum white blood cell (WBC) count. Elevated systemic inflammatory insult may contribute to impaired lung function, such as obstructive or restrictive lung disease. The aim of our study is to investigate the correlation between WBC count and pulmonary function. Eligible participants aged ≥18 years (n=16 312) were enrolled from the United States National Health and Nutrition Examination Survey III, 1988-1994. Pertinent information including pulmonary function test, demographics, WBC count, glucose, C-reactive protein and a personal health questionnaire were obtained for subjects without known pulmonary diseases. White blood cell counts were classified into quartiles over the normal range. Multiple hierarchical regression models and trends testing were used to assess the correlation between WBC counts and pulmonary function tests. In the unadjusted mode of quartile-based analysis, the beta coefficients interpreted as the differences in FEV1% predicted upon comparing subjects in the upper three quartiles of WBC count to those in the lowest quartile were -0.007, -0.022 and -0.041 (P<0.001). After adjusting for multiple pertinent covariates, inverse association between quartiles of WBC count and FEV1% predicted remained essentially unchanged. The negative trends between FEV1% predicted and WBC count quartiles in the stratified comparison with extended-model approach were statistically significant (P for trends<0.001) in quartile-based multiple linear regression. Elevated WBC count is independently associated with declined pulmonary function. It may be a simple, accessible and inexpensive indicator of changes in pulmonary function.

  7. Serum white blood cell count and pulmonary function test are negatively associated.

    PubMed

    Yang, Hui-Fang; Kao, Tung-Wei; Wang, Chung-Ching; Peng, Tao-Chun; Chang, Yaw-Wen; Chen, Wei-Liang

    2015-07-22

    A variety of inflammatory disorders influence the serum white blood cell (WBC) count. Elevated systemic inflammatory insult may contribute to impaired lung function, such as obstructive or restrictive lung disease. The aim of our study is to investigate the correlation between WBC count and pulmonary function. Eligible participants aged ≥ 18 years (n = 16 312) were enrolled from the United States National Health and Nutrition Examination Survey III, 1988-1994. Pertinent information including pulmonary function test, demographics, WBC count, glucose, C-reactive protein and a personal health questionnaire were obtained for subjects without known pulmonary diseases. White blood cell counts were classified into quartiles over the normal range. Multiple hierarchical regression models and trends testing were used to assess the correlation between WBC counts and pulmonary function tests. In the unadjusted mode of quartile-based analysis, the beta coefficients interpreted as the differences in FEV1% predicted upon comparing subjects in the upper three quartiles of WBC count to those in the lowest quartile were - 0.007, - 0.022 and - 0.041 (P < 0.001). After adjusting for multiple pertinent covariates, inverse association between quartiles of WBC count and FEV1% predicted remained essentially unchanged. The negative trends between FEV1% predicted and WBC count quartiles in the stratified comparison with extended-model approach were statistically significant (P for trends < 0.001) in quartile-based multiple linear regression. Elevated WBC count is independently associated with declined pulmonary function. It may be a simple, accessible and inexpensive indicator of changes in pulmonary function.

  8. Patient-Specific Computational Modeling of Blood Flow in the Pulmonary Arterial Circulation

    PubMed Central

    Kheyfets, Vitaly O.; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J.; Finol, Ender A.

    2015-01-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right heart catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear Stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R2 = 0.77, P < 0.05) and arterial compliance (C) (R2 = 0.63, P < 0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  9. Patient-specific computational modeling of blood flow in the pulmonary arterial circulation.

    PubMed

    Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A

    2015-07-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  10. 129Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129Xe NMR

    PubMed Central

    Norquay, Graham; Leung, General; Stewart, Neil J.; Wolber, Jan

    2016-01-01

    Purpose To evaluate the dependency of the 129Xe‐red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129Xe NMR. Methods Hyperpolarized 129Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129Xe. Results The 129Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7–10 % in RBC oxygenation. The 129Xe‐RBC signal amplitude showed a modulation with the same frequency as the 129Xe‐RBC chemical shift. Conclusion The feasibility of using the 129Xe‐RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129Xe‐RBC signal and 129Xe‐RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399–1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27062652

  11. (129) Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized (129) Xe NMR.

    PubMed

    Norquay, Graham; Leung, General; Stewart, Neil J; Wolber, Jan; Wild, Jim M

    2017-04-01

    To evaluate the dependency of the (129) Xe-red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized (129) Xe NMR. Hyperpolarized (129) Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized (129) Xe. The (129) Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the (129) Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7-10 % in RBC oxygenation. The (129) Xe-RBC signal amplitude showed a modulation with the same frequency as the (129) Xe-RBC chemical shift. The feasibility of using the (129) Xe-RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between (129) Xe-RBC signal and (129) Xe-RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399-1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  12. Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease

    PubMed Central

    Duvoix, Annelyse; Dickens, Jenny; Haq, Imran; Mannino, David; Miller, Bruce; Tal-Singer, Ruth

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV1. However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker. Methods Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality. Results There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. Conclusions Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. PMID:22744884

  13. Exogenous ghrelin improves blood flow distribution in pulmonary hypertension-assessed using synchrotron radiation microangiography.

    PubMed

    Schwenke, Daryl O; Gray, Emily A; Pearson, James T; Sonobe, Takashi; Ishibashi-Ueda, Hatsue; Campillo, Isabel; Kangawa, Kenji; Umetani, Keiji; Shirai, Mikiyasu

    2011-09-01

    Ghrelin has cardioprotective properties and, recently, has been shown to improve endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in peripheral vascular disease. Recently, we reported that ghrelin attenuates pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized in this study may be via suppression of the ET-1 pathway. We also aimed to determine whether ghrelin's ability to prevent alterations of the ET-1 pathway also prevented adverse changes in pulmonary blood flow distribution associated with PH. Sprague-Dawley rats were exposed to CH (10% O(2) for 2 weeks) with daily subcutaneous injections of ghrelin (150 μg/kg) or saline. Utilizing synchrotron radiation microangiography, we assessed pulmonary vessel branching structure, which is indicative of blood flow distribution, and dynamic changes in vascular responsiveness to (1) ET-1 (1 nmol/kg), (2) the ET-1(A) receptor antagonist, BQ-123 (1 mg/kg), and (3) ACh (3.0 μg kg⁻¹ min⁻¹). CH impaired blood flow distribution throughout the lung. However, this vessel "rarefaction" was attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated vasoconstriction, and (3) reduced pulmonary vascular remodeling and right ventricular hypertrophy-all adverse consequences associated with CH. These results highlight the beneficial effects of ghrelin for maintaining optimal lung perfusion in the face of a hypoxic insult. Further research is now required to establish whether ghrelin is also an effective therapy for restoring normal pulmonary hemodynamics in patients that already have established PH.

  14. Blood lead levels of the battery and exhaust workers and their pulmonary function tests.

    PubMed

    Bagci, C; Bozkurt, A I; Cakmak, E A; Can, S; Cengiz, B

    2004-06-01

    In an attempt to understand the impact of inhaled lead on the pulmonary functions, we assessed the blood lead levels and pulmonary functions of the battery and exhaust workers who are potential candidates for lead inhalation. The hospital staff served as control group. The measurements of lead levels were performed using atomic absorption spectrophotometry. Pulmonary function tests (PFTs) were performed using a portable spirometer. The blood lead levels of the battery workers, exhaust workers and controls were found to be 36.83, 26.94 and 14.81 microg/dl, respectively. The values of the workers were significantly higher than the controls (p < 0.001). The lead levels of the battery workers were also significantly higher than the exhaust workers (p < 0.001). PFT results (maximum voluntary ventilation, forced expiration flow and first forced expiration volume values of the workers) were significantly worse than the controls, and their pulmonary function test results were consistent with restrictive problems in the airways.

  15. Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation.

    PubMed

    Honda, Takashi; Itatani, Keiichi; Takanashi, Manabu; Kitagawa, Atsushi; Ando, Hisashi; Kimura, Sumito; Nakahata, Yayoi; Oka, Norihiko; Miyaji, Kagami; Ishii, Masahiro

    2016-11-01

    In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

    PubMed

    van Zeller, Mafalda; Mota, Patrícia Caetano; Amorim, Adelina; Viana, Paulo; Martins, Paula; Gaspar, Luís; Hespanhol, Venceslau; Gomes, Isabel

    2012-01-01

    Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

  17. Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Hlastala, M. P.

    1998-01-01

    We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

  18. Spatial distribution of pulmonary blood flow in dogs in increased force environments

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. F.; Ritman, E. L.; Chevalier, P. A.; Sass, D. J.; Wood, E. H.

    1978-01-01

    Spatial distribution of pulmonary blood flow during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: (1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but (2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and (3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax.

  19. Spatial distribution of pulmonary blood flow in dogs in increased force environments

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. F.; Ritman, E. L.; Chevalier, P. A.; Sass, D. J.; Wood, E. H.

    1978-01-01

    Spatial distribution of pulmonary blood flow during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: (1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but (2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and (3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax.

  20. Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

    NASA Technical Reports Server (NTRS)

    Walther, S. M.; Domino, K. B.; Hlastala, M. P.

    1998-01-01

    We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

  1. Major contribution of central pulmonary reservoir discharge to increased pulmonary arterial diastolic blood flow after birth in near-term lambs.

    PubMed

    Smolich, Joseph J; Mynard, Jonathan P

    2016-10-01

    Recent fetal lamb data have suggested that the pulmonary trunk (PT) region displays a reservoir function and that a pharmacologically induced fall in pulmonary vascular resistance (PVR) increases and redistributes diastolic discharge from this central pulmonary reservoir toward the lungs, thereby producing a positive diastolic offset in the pulmonary arterial (PA) blood flow profile. As a similar offset in PA flow characteristically occurs after birth, this study tested the hypotheses that 1) central pulmonary reservoir discharge is both redistributed toward the lungs and increased in magnitude during the birth transition and 2) discharge from this reservoir constitutes a major component of increased PA diastolic blood flow after birth. Six anesthetized near-term fetal lambs were instrumented with PT, ductal and left PA transit-time flow probes, and aortic, PT and left atrial catheters. Hemodynamic data were recorded in fetuses and at regular intervals during 2-h mechanical ventilation following cesarean section delivery. Diastolic PA blood flow rose from near zero in fetuses to 468 ± 188 ml/min by 15 min (P < 0.001). Central pulmonary reservoir discharge in fetuses (99 ± 44 ml/min) passed primarily right-to-left across the ductus. However, this reservoir discharge redistributed entirely to the lungs by 1 min after birth, and then doubled to a peak of 214 ± 167 ml/min at 15 min (P < 0.001). Reservoir discharge subsequently stabilized at 151 ± 60 ml/min at 30-120 min, which comprised ∼50% of diastolic and ∼20% of mean PA blood flow. These findings suggest that enhanced diastolic central pulmonary reservoir discharge plays a major role in supporting an increased pulmonary perfusion after birth.

  2. Hemodilution during venous gas embolization improves gas exchange, without altering V(A)/Q or pulmonary blood flow distributions.

    PubMed

    Deem, S; McKinney, S; Polissar, N L; Hedges, R G; Swenson, E R

    1999-12-01

    Isovolemic anemia results in improved gas exchange in rabbits with normal lungs but in relatively poorer gas exchange in rabbits with whole-lung atelectasis. In the current study, the authors characterized the effects of hemodilution on gas exchange in a distinct model of diffuse lung injury: venous gas embolization. Twelve anesthetized rabbits were mechanically ventilated at a fixed rate and volume. Gas embolization was induced by continuous infusion of nitrogen via an internal jugular venous catheter. Serial hemodilution was performed in six rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; six rabbits were followed as controls over time. Measurements included hemodynamic parameters and blood gases, ventilation-perfusion (V(A)/Q) distribution (multiple inert gas elimination technique), pulmonary blood flow distribution (fluorescent microspheres), and expired nitric oxide (NO; chemoluminescence). Venous gas embolization resulted in a decrease in partial pressure of arterial oxygen (PaO2) and an increase in partial pressure of arterial carbon dioxide (PaCO2), with markedly abnormal overall V(A)/Q distribution and a predominance of high V(A)/Q areas. Pulmonary blood flow distribution was markedly left-skewed, with low-flow areas predominating. Hematocrit decreased from 30+/-1% to 11+/-1% (mean +/- SE) with hemodilution. The alveolar-arterial PO2 (A-aPO2) difference decreased from 375+/-61 mmHg at 30% hematocrit to 218+/-12.8 mmHg at 15% hematocrit, but increased again (301+/-33 mmHg) at 11% hematocrit. In contrast, the A-aPO2 difference increased over time in the control group (P < 0.05 between groups over time). Changes in PaO2 in both groups could be explained in large part by variations in intrapulmonary shunt and mixed venous oxygen saturation (SvO2); however, the improvement in gas exchange with hemodilution was not fully explained by significant changes in V(A)/Q or pulmonary blood flow distributions, as quantitated

  3. Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

    PubMed

    Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

    2016-12-01

    Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with

  4. A modified Verhoeff's elastin histochemical stain to enable pulmonary arterial hypertension model characterization.

    PubMed

    Percival, K R; Radi, Z A

    2016-02-11

    Optimal histochemical staining is critical to ensure excellent quality stained sections to enable light microscopic and histomorphometric image analysis.  Verhoeff-van Gieson is the most widely used histochemical stain for the visualization of vascular elastic fibers. However, it is notoriously difficult to differentiate fine elastic fibers of small vasculature to enable histomorphometric image analysis of vasculature size characterization especially in organs such as the lung. A tissue fixation regime of 10% neutral buffered formalin with subsequent fixation in 70% ethanol further compounds the problem of small vessel staining and identification.  Therefore, a modified Verhoeff's elastin stain was developed as a reliable method to optimally highlight the internal and external elastic lamina of small arteries (50-100 µm) and intra-acinar vessels (10-50 µm) in 3 µm thick lung tissue sections from models of pulmonary arterial hypertension.  This modified Verhoeff's elastin stain demonstrated optimal staining of fine elastic fibers of pulmonary blood vessels. As a result, high-quality histomorphometric image analysis evaluation of vessel wall thickness in small arteries and intra-acinar vessels was successfully accomplished.  In conclusion, modification of the standard Verhoeff-van Gieson histochemical stain is needed to visualize small caliber vessels' elastic fibers especially in tissues not fixed in 10% neutral buffered formalin only.

  5. Regional pulmonary blood flow in sitting and supine man during and after acute hypoxia

    PubMed Central

    Dawson, Arthur

    1969-01-01

    Regional pulmonary blood flow was measured by external counting of intravenously injected 133Xe during 20 min of breathing 14.2% oxygen and during 20 min of recovery from hypoxia. 16 normal human volunteers were studied, nine sitting and seven supine. During hypoxia there was a slight but significant increase in relative perfusion of the upper portions of the lungs in both the sitting and supine subjects. During recovery from hypoxia, blood flow distribution differed significantly from the control. The erect subjects showed increased relative perfusion of the lung bases and the supine subjects showed increased relative perfusion of the upper zones. Comparison of the distribution of inhaled and intravenously injected isotope showed that in the sitting subjects the altered distribution during hypoxia tended to make alveolar oxygen tension more uniform. In the supine subjects, however, the shift in blood flow increased the perfusion of the regions with the lowest ventilation/perfusion, tending to accentuate uneven alveolar oxygen tension. Therefore it does not seem that the altered blood flow distribution during hypoxia was due to selective vasoconstriction in the regions of lowest alveolar oxygen tension, but rather that vasoconstriction was greatest in the lower lung zones because the vessels there are more responsive to hypoxia. During mild acute hypoxia, vasoconstrictor tone does not seem to effectively match ventilation and perfusion. The altered distribution of pulmonary blood flow during recovery from hypoxia suggests the occurrence of posthypoxic vasodilation. Failure to consider this possibility may lead to erroneous interpretation of pulmonary hemodynamic measurements made after the inspired oxygen concentration has been changed. PMID:5764012

  6. Pulmonary Hypertension in Lambs Transfused with Stored Blood is Prevented by Breathing Nitric Oxide

    PubMed Central

    Baron, David M.; Yu, Binglan; Lei, Chong; Bagchi, Aranya; Beloiartsev, Arkadi; Stowell, Christopher P.; Steinbicker, Andrea U.; Malhotra, Rajeev; Bloch, Kenneth D.; Zapol, Warren M.

    2012-01-01

    Background During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect. Methods We developed a model of autologous stored blood transfusion in lambs (n=36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of NG-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm). Results Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean±SD, 148±20 versus 41±13 mg/dl, respectively, P<0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13±1 to 18±1 mmHg (P<0.001) and was associated with increased plasma hemoglobin concentrations. NG-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response. Conclusions Our results suggest that patients with reduced vascular nitric oxide levels due to endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC. PMID:22293717

  7. Assessment of differential pulmonary blood flow using perfusion magnetic resonance imaging: comparison with radionuclide perfusion scintigraphy.

    PubMed

    Molinari, Francesco; Fink, Christian; Risse, Frank; Tuengerthal, Siegfried; Bonomo, Lorenzo; Kauczor, Hans-Ulrich

    2006-08-01

    We sought to assess the agreement between lung perfusion ratios calculated from pulmonary perfusion magnetic resonance imaging (MRI) and those calculated from radionuclide (RN) perfusion scintigraphy. A retrospective analysis of MR and RN perfusion scans was conducted in 23 patients (mean age, 60 +/- 14 years) with different lung diseases (lung cancer = 15, chronic obstructive pulmonary disease = 4, cystic fibrosis = 2, and mesothelioma = 2). Pulmonary perfusion was assessed by a time-resolved contrast-enhanced 3D gradient-echo pulse sequence using parallel imaging and view sharing (TR = 1.9 milliseconds; TE = 0.8 milliseconds; parallel imaging acceleration factor = 2; partition thickness = 4 mm; matrix = 256 x 96; in-plane spatial resolution = 1.87 x 3.75 mm; scan time for each 3D dataset = 1.5 seconds), using gadolinium-based contrast agents (injection flow rate = 5 mL/s, dose = 0.1 mmol/kg of body weight). The peak concentration (PC) of the contrast agent bolus, the pulmonary blood flow (PBF), and blood volume (PBV) were computed from the signal-time curves of the lung. Left-to-right ratios of pulmonary perfusion were calculated from the MR parameters and RN counts. The agreement between these ratios was assessed for side prevalence (sign test) and quantitatively (Deming-regression). MR and RN ratios agreed on side prevalence in 21 patients (91%) with PC, in 20 (87%) with PBF, and in 17 (74%) with PBV. The MR estimations of left-to-right perfusion ratios correlated significantly with those of RN perfusion scans (P < 0.01). The correlation was higher using PC (r = 0.67) and PBF (r = 0.66) than using PBV (r = 0.50). The MR ratios computed from PBF showed the highest accuracy, followed by those from PC and PBV. Independently from the MR parameter used, in some patients the quantitative difference between the MR and RN ratios was not negligible. Pulmonary perfusion MRI can be used to assess the differential blood flow of the lung. Further studies in a larger group

  8. Assessing the calf pulmonary function during a long-term biventricular assist device study with a centrifugal blood pump.

    PubMed

    Nonaka, Kenji; Linneweber, Joerg; Ichikawa, Seiji; Kawahito, Shinji; Motomura, Tadashi; Ishitoya, Hiroshi; Oestmann, Daniel; Glueck, Julia; Nosé, Yukihiko

    2002-11-01

    Pulmonary congestion due to inappropriate pump flow management is one major problem necessary to avoid during long-term biventricular assist device (BVAD) implantation. Our objective was to assess the effects of pulmonary arterial flow rate and flow rates of both (right and left) bypass pumps. Six healthy calves, which had been implanted with a BVAD system, were selected for this retrospective study. Pulmonary artery flows, both pump flow rates, oxygen saturation of the arterial blood, and pulmonary arterial pressures were assessed as parameters of pulmonary function as was routine clinical evaluation of respiratory rate and character and chest auscultation. The average pulmonary artery flow rate (PAF), systolic pressure of pulmonary artery (sPAP), and oxygen saturation were 148.8 ml/kg per min, 35.1 mm Hg, and 95.3%, respectively. Pulmonary dysfunction occurred in one case, in which the mean PAF, sPAP, and oxygen saturation were 169 ml/kg per min, 66.1 mm Hg, and 90.9%, respectively. The ratio for the right/left pump flow rate (R/L ratio) for the case having pulmonary dysfunction was 1.57 even though the ratio for the other cases was less than 1. Maintaining an R/L ratio less than 1 and/or PAF less than 160 ml/kg per min and PAP less than 50 mm Hg is recommended as the initial conditions to target to avoid pulmonary dysfunction during a BVAD implantation with a beating heart condition.

  9. Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

    PubMed

    Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

    2015-12-01

    Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

  10. Age-dependent neutrophil and blood flow responsiveness in acute pulmonary inflammation in rabbits.

    PubMed

    Hyde, D M; Downey, G P; Tablin, F; Rosengren, S; Giclas, P C; Henson, P M; Worthen, G S

    1997-03-01

    Diminished ability of neonatal neutrophils to orient and move in a chemotactic gradient has been linked to compromised pulmonary host defense. We investigated whether deficiency of neonatal neutrophil function in vitro was evident in acute pulmonary inflammation. Analysis of neutrophils in vitro showed impaired chemotaxis in 4-wk-old compared with adult rabbits. In vivo-directed migration of labeled neutrophils into the alveolar space of adult rabbits in response to C5f instillation was significantly less for neutrophils donated from 4-wk-old rabbits compared with those from adults. In contrast, there were no differences in the alveolar accumulation of 4-wk-old and adult labeled neutrophils in 4-wk-old rabbits in response to C5f instillation, although the response showed a shorter time course than seen in adult rabbits. Adult rabbits diverted 46% of the blood away from the right cranial lung lobe, whereas 4-wk-old rabbits showed no change in blood flow after C5f instillation. Megakaryocytes (a source of blood flow mediators) were 3.2-fold greater in adult compared with 4-wk-old lung. These data suggest that the lack of blood flow diversion from inflamed neonatal lung increases neutrophil migration into alveoli, allowing for preservation of an inflammatory response despite neutrophil deficiencies in chemotaxis.

  11. Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

    NASA Astrophysics Data System (ADS)

    Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

    2015-11-01

    Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

  12. Phasic reflux of pulmonary blood flow in atelectasis: influence of systemic PO2.

    PubMed

    Newell, J C; Levitzky, M G; Krasney, J A; Dutton, R E

    1976-06-01

    In 16 dogs ventilated with 100% O2, control blood flow to the left lung was 35 +/- 2% of aortic flow. When left lung atelectasis was induced, left pulmonary artery flow fell to 19 +/- 2% of aortic flow. A large retrograde component of flow developed in this pulmonary artery, suggesting that blood flows into the pulmonary arteries of both lungs during systole, but flows back out of the collapsed lung and into the uncollapsed lung during diastole. Systemic PaO2 remained above 78 mmHg. Subsequently, when the ventilation of the right lung was changed from oxygen to room air, systemic PaO2 fell to 64 +/- 3 mmHg and atelectatic left lung flow rose from 19 +/- 2% to 28 +/- 2% f aortic flow. This was associated with a reduction in reflux from the atelectatic lung. These results suggest that the attenuation of flow to an atelectatic lung is more pronounced if systemic normoxemia is maintained by adequate oxygenation of the normal lung.

  13. Changes in cerebral oxygen saturation and blood flow during hypoxic gas ventilation therapy in HLHS and CoA/IAA complex with markedly increased pulmonary blood flow.

    PubMed

    Toiyama, Kentaro; Hamaoka, Kenji; Oka, Tatsujiro; Kobayashi, Naho; Noritake, Kanae; Kato, Ryuichi; Kawai, Yoko; Ozawa, Seiichiro; Nishida, Masashi; Itoi, Toshiyuki

    2010-10-01

    Hypoxic gas ventilation therapy has recently been performed to prevent post-birth increased pulmonary blood flow in cases of congenital heart diseases with increased pulmonary blood flow. However, how the oxygen supply to the tissues changes during breathing a hypoxic gas mixture, remains unknown. The changes in cerebral oxygen saturation and blood supply during hypoxic gas ventilation therapy using a nitrogen gas mixture were studied. Cerebral regional oxygen saturation (cerebral rSO(2)) was measured by near-infrared spectroscopy, and changes in middle cerebral artery (MCA) blood flow and an index of vascular resistance (RI) were assessed in 8 consecutive patients having congenital heart diseases with increased pulmonary blood flow. In all patients, urinary volume increased significantly, and the respiratory rate showed a clear decrease. Percutaneous oxygen saturation showed no significant change. The average of cerebral rSO(2) was 67.3% before hypoxic gas ventilation, but increased to 69.4%, 69.1%, and 70.7% within 1, 12, and 24 h after initiation of treatment, respectively. MCA blood flow significantly increased in the diastolic phase, and RI significantly improved from 0.80 to 0.68 within 12 h after initiation of therapy. These results indicate that hypoxic gas ventilation therapy does not decrease cerebral oxygen saturation, but safely improves the cerebral blood supply in cases of congenital heart diseases with increased pulmonary blood flow. 

  14. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation.

    PubMed

    Qureshi, M Umar; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S; Olufsen, Mette S; Hill, N A

    2014-10-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung.

  15. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

    PubMed Central

    Qureshi, M. Umar; Vaughan, Gareth D.A.; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S.; Olufsen, Mette S.; Hill, N.A.

    2014-01-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen and coworkers (Ottesen et al., 2003; Olufsen et al., 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50µm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment of circulatory diseases within the lung. PMID:24610385

  16. Pulmonary edema and blood volume after aneurysmal subarachnoid hemorrhage: a prospective observational study

    PubMed Central

    2010-01-01

    Introduction Pulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED. Methods Circulating blood volume (CBV) was determined daily during the first 10 days after SAH by means of pulse dye densitometry. CBV of 60-80 ml/kg was considered normal. PED was diagnosed from clinical signs and characteristic bilateral pulmonary infiltrates on the chest radiograph. We compared CBV, cardiac index, and fluid balance between patients with and without PED with weighted linear regression, taking into account only measurements from the first day after SAH through to the day on which PED was diagnosed. Differences were adjusted for age, bodyweight, and clinical condition. Results In total, 102 patients were included, 17 of whom developed PED after a mean of 4 days after SAH. Patients developing PED had lower mean CBV (56.6 ml/kg) than did those without PED (66.8 ml/kg). The mean difference in CBV was -11.3 ml/kg (95% CI, -16.5 to -6.1); adjusted mean difference, -8.0 ml/kg (95% CI, -14.0 to -2.0). After adjusting, no differences were found in cardiac index or fluid balance between patients with and without PED. Conclusions SAH patients developing pulmonary edema have a lower blood volume than do those without PED and are hypovolemic. Measures taken to counteract pulmonary edema must be balanced against the risk of worsening hypovolemia. Trial registration NTR1255. PMID:20331893

  17. The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils

    PubMed Central

    Rogliani, Paola; Puxeddu, Ermanno; Ciaprini, Chiara; Ora, Josuel; Onorato, Angelo; Pezzuto, Gabriella; Calzetta, Luigino

    2016-01-01

    Only very few studies have investigated the influence of eosinophils on the functional progression of COPD. We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]). We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years. The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group. The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively. PMID:27822474

  18. Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.

    PubMed

    Sánchez Crespo, Alejandro; Hallberg, Jenny; Lundberg, Jon O; Lindahl, Sten G E; Jacobsson, Hans; Weitzberg, Eddie; Nyrén, Sven

    2010-01-01

    There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution. In the sitting upright position, subjects first breathed NO free air through the mouth followed by the administration of the first tracer. Subjects then switched to either nasal breathing or oral breathing with the addition of exogenous NO-enriched air followed by the administration of the second tracer. Compared with oral breathing, nasal breathing induced a blood flow redistribution of approximately 4% of the total perfusion in the caudal to cranial and dorsal to ventral directions. For low perfused lung regions like the apical region, this represents a net increase of 24% in blood flow. Similar effects were obtained with the addition of exogenous NO during oral breathing, indicating that NO and not the breathing condition was responsible for the blood flow redistribution. In conclusion, these results provide evidence that autoinhalation of endogenous NO from the nasal airways may ameliorate the influence of gravity on pulmonary blood flow distribution in the upright position. The presence of nasal NO only in humans and higher primates suggest that it may be an important part of the adaptation to bipedalism.

  19. Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution.

    PubMed

    West, John B

    2009-12-01

    Two opposing selective pressures have shaped the evolution of the structure of the blood-gas barrier in air breathing vertebrates. The first pressure, which has been recognized for 100 years, is to facilitate diffusive gas exchange. This requires the barrier to be extremely thin and have a large area. The second pressure, which has only recently been appreciated, is to maintain the mechanical integrity of the barrier in the face of its extreme thinness. The most important tensile stress comes from the pressure within the pulmonary capillaries, which results in a hoop stress. The strength of the barrier can be attributed to the type IV collagen in the extracellular matrix. In addition, the stress is minimized in mammals and birds by complete separation of the pulmonary and systemic circulations. Remarkably, the avian barrier is about 2.5 times thinner than that in mammals and also is much more uniform in thickness. These advantages for gas exchange come about because the avian pulmonary capillaries are unique among air breathers in being mechanically supported externally in addition to the strength that comes from the structure of their walls. This external support comes from epithelial plates that are part of the air capillaries, and the support is available because the terminal air spaces in the avian lung are extremely small due to the flow-through nature of ventilation in contrast to the reciprocating pattern in mammals.

  20. Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution

    PubMed Central

    2009-01-01

    Two opposing selective pressures have shaped the evolution of the structure of the blood-gas barrier in air breathing vertebrates. The first pressure, which has been recognized for 100 years, is to facilitate diffusive gas exchange. This requires the barrier to be extremely thin and have a large area. The second pressure, which has only recently been appreciated, is to maintain the mechanical integrity of the barrier in the face of its extreme thinness. The most important tensile stress comes from the pressure within the pulmonary capillaries, which results in a hoop stress. The strength of the barrier can be attributed to the type IV collagen in the extracellular matrix. In addition, the stress is minimized in mammals and birds by complete separation of the pulmonary and systemic circulations. Remarkably, the avian barrier is about 2.5 times thinner than that in mammals and also is much more uniform in thickness. These advantages for gas exchange come about because the avian pulmonary capillaries are unique among air breathers in being mechanically supported externally in addition to the strength that comes from the structure of their walls. This external support comes from epithelial plates that are part of the air capillaries, and the support is available because the terminal air spaces in the avian lung are extremely small due to the flow-through nature of ventilation in contrast to the reciprocating pattern in mammals. PMID:19793953

  1. Pulmonary fibrosis: tissue characterization using late-enhanced MRI compared with unenhanced anatomic high-resolution CT

    PubMed Central

    Lavelle, Lisa P.; Brady, Darragh; McEvoy, Sinead; Murphy, David; Gibney, Brian; Gallagher, Annika; Butler, Marcus; Shortt, Fionnula; McMullen, Marie; Fabre, Aurelie; Lynch, David A.; Keane, Michael P.; Dodd, Jonathan D.

    2017-01-01

    PURPOSE We aimed to prospectively evaluate anatomic chest computed tomography (CT) with tissue characterization late gadolinium-enhanced magnetic resonance imaging (MRI) in the evaluation of pulmonary fibrosis (PF). METHODS Twenty patients with idiopathic pulmonary fibrosis (IPF) and twelve control patients underwent late-enhanced MRI and high-resolution CT. Tissue characterization of PF was depicted using a segmented inversion-recovery turbo low-angle shot MRI sequence. Pulmonary arterial blood pool nulling was achieved by nulling main pulmonary artery signal. Images were read in random order by a blinded reader for presence and extent of overall PF (reticulation and honeycombing) at five anatomic levels. Overall extent of IPF was estimated to the nearest 5% as well as an evaluation of the ratios of IPF made up of reticulation and honeycombing. Overall grade of severity was dependent on the extent of reticulation and honeycombing. RESULTS No control patient exhibited contrast enhancement on lung late-enhanced MRI. All IPF patients were identified with late-enhanced MRI. Mean signal intensity of the late-enhanced fibrotic lung was 31.8±10.6 vs. 10.5±1.6 for normal lung regions, P < 0.001, resulting in a percent elevation in signal intensity from PF of 204.8%±90.6 compared with the signal intensity of normal lung. The mean contrast-to-noise ratio was 22.8±10.7. Late-enhanced MRI correlated significantly with chest CT for the extent of PF (R=0.78, P = 0.001) but not for reticulation, honeycombing, or coarseness of reticulation or honeycombing. CONCLUSION Tissue characterization of IPF is possible using inversion recovery sequence thoracic MRI. PMID:28067202

  2. Comparative imaging of differential pulmonary blood flow in patients with congenital heart disease: magnetic resonance imaging versus lung perfusion scintigraphy.

    PubMed

    Roman, Kevin S; Kellenberger, Christian J; Farooq, Saqba; MacGowan, Christopher K; Gilday, David L; Yoo, Shi-Joon

    2005-03-01

    Lung perfusion scintigraphy is considered the gold standard to assess differential pulmonary blood flow while magnetic resonance (MR) has been shown to be an accurate alternative in some studies. The purpose of the study was to assess the accuracy of phase contrast magnetic resonance (PC-MR) in measuring pulmonary blood flow ratio compared with lung perfusion scintigraphy in patients with complex pulmonary artery anatomy or pulmonary hypertension and to document reasons for discrepant results. We identified 25 cases of congenital heart disease between January 2000 and 2003, in whom both techniques of assessing pulmonary blood flow were performed within a 6-month period without an interim surgical or transcatheter intervention. The study group included cases with branch pulmonary artery stenosis, intracardiac shunts, single ventricle circulation, pulmonary venous anomalies and conotruncal defects. The mean age at study was 5.7 years (range 0.33-12) with a mean weight of 20.3 kg (range 6.5-53.6). The two methods were compared using a Bland-Altman analysis, and the Pearson correlation coefficient was calculated using the lung scan as the gold standard. Discrepant results were examined by reviewing the source images to elucidate reasons for error by MR. Bland-Altman analysis comparing right pulmonary artery (RPA) blood flow percentage, as measured by each modality, showed a mean difference of 1.43+/-9.8 (95% limits of agreement: -17.8, 20.6) with a correlation coefficient of r=0.84, P<0.0001. In six (24%) cases a large difference (>10%) was found with a mean difference between techniques of 17.9%. The reasons for discrepant results included MR artifacts, dephasing owing to turbulent flow, site of data acquisition and lobar lung collapse. When using PC-MR to assess pulmonary blood flow ratio, important technical errors occur in a significant proportion of patients who have abnormal pulmonary artery anatomy or pulmonary hypertension. If these technical errors are avoided

  3. Blood and tissue distribution of posaconazole in a rat model of invasive pulmonary aspergillosis.

    PubMed

    Cendejas-Bueno, E; Forastiero, A; Ruiz, I; Mellado, E; Gavaldà, J; Gomez-Lopez, A

    2017-02-01

    Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue. The PK behavior of posaconazole in this particular experimental model is similar to that observed in humans. Thus, we believe this model could be a valid tool to evaluate posaconazole exposure-response relationship.

  4. An analysis of estimation of pulmonary blood flow by the single-breath method

    NASA Technical Reports Server (NTRS)

    Srinivasan, R.

    1986-01-01

    The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

  5. An analysis of estimation of pulmonary blood flow by the single-breath method

    NASA Technical Reports Server (NTRS)

    Srinivasan, R.

    1986-01-01

    The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

  6. Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

    PubMed

    Maissen-Villiger, Carla A; Schweighauser, Ariane; van Dorland, H Anette; Morel, Claudine; Bruckmaier, Rupert M; Zurbriggen, Andreas; Francey, Thierry

    2016-01-01

    Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options

  7. Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Cukic, Vesna

    2015-01-01

    Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary disease (COPD). Material and methods: We observed 160 patients with COPD treated in Clinic for Pulmonary Diseases and TB “Podhrastovi” Sarajevo during three years :from 2012 to 2014. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood PMNL was measured in a stable state of disease at the begging and at the end of investigation. Results: The number of blood PMNL was significantly greater in patients with 3 or more exacerbations per one year (p <0.01). Patients with BHR had significantly greater number blood PMNL than patients without BHR (p< 0.05). Patients with 3 exacerbations per year had a statistically significant increase of number of PMNL between first and last examination (p<0.01). Conclusion: There is statistically significant correlation between the number of blood PMNL and the level of BHR in COPD, but future examination need to be done to determine real role and mode of action of PMNL for these processes. PMID:26543311

  8. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    EPA Science Inventory

    Abstract
    Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  9. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    EPA Science Inventory

    Abstract
    Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  10. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    PubMed

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  11. Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

    PubMed

    Richter, Torsten; Bergmann, Ralf; Musch, Guido; Pietzsch, Jens; Koch, Thea

    2015-01-01

    Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

  12. Chemoreceptor influence on pulmonary blood flow during unilateral hypoxia in dogs.

    PubMed

    Levitzky, M G; Newell, J C; Krasney, J A; Dutton, R E

    1977-12-01

    Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta, QT. Following 10 min of bilateral 100% O2, QL was 42.5 +/- 7% of QT. When 6% O2, was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O2, PaO2 was above 70 mm Hg and QL fell to 24.5 +/- 5% of QT. Room air was then used to ventilate the right lung while the left lung remained on 6% O2. This caused PaO2 to fall to 42.3 +/- 3 MM Hg and QL to rise to 38.3 +/- 6% QT. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

  13. Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease.

    PubMed

    Brüske, Irene; Hampel, Regina; Socher, Martin M; Rückerl, Regina; Schneider, Alexandra; Heinrich, Joachim; Oberdörster, Günter; Wichmann, H-Erich; Peters, Annette

    2010-02-01

    Epidemiologic studies report associations between particulate air pollution and increased mortality from pulmonary diseases. This study was performed to examine whether the exposure to ambient gaseous and particulate air pollution leads to an alteration of the differential white blood cell count in patients with chronic pulmonary diseases like chronic bronchitis, chronic obstructive pulmonary disease, and asthma. A prospective panel study was conducted in Erfurt, Eastern Germany, with 12 repeated differential white blood cell counts in 38 males with chronic pulmonary diseases. Hourly particulate and gaseous air pollutants and meteorological data were acquired. Mixed models with a random intercept adjusting for trend, meteorology, weekday, and other risk variables were used. In this explorative analysis, we found an immediate decrease of polymorphonuclear leukocytes in response to an increase of most gaseous and particulate pollutants. Lymphocytes increased within 24 h in association with all gaseous pollutants but showed only minor effects in regard to particulate air pollution. Monocytes showed an increase associated with ultrafine particles, and nitrogen monoxide. The effect had two peaks in time, one 0-23 h before blood withdrawal and a second one with a time lag of 48-71 h. The increase of particulate and gaseous air pollution was associated with multiple changes in the differential white blood cell count in patients with chronic pulmonary diseases.

  14. Impact of Ambient Air Pollution on the Differential White Blood Cell Count in Patients with Chronic Pulmonary Disease

    PubMed Central

    Brüske, Irene; Hampel, Regina; Socher, Martin M.; Rückerl, Regina; Schneider, Alexandra; Heinrich, Joachim; Oberdörster, Günter; Wichmann, H.-Erich; Peters, Annette

    2013-01-01

    Epidemiologic studies report associations between particulate air pollution and increased mortality from pulmonary diseases.To examine whether the exposure to ambient gaseous and particulate air pollution leads to an alteration of the differential white blood cell count in patients with chronic pulmonary diseases like chronic bronchitis, chronic obstructive pulmonary disease, and asthma. A prospective panel study was conducted in Erfurt, Eastern Germany, with 12 repeated differential white blood cell counts in 38 males with chronic pulmonary diseases. Hourly particulate and gaseous air pollutants and meteorological data were acquired. Mixed models with a random intercept adjusting for trend, meteorology, weekday, and other risk variables were used. In this explorative analysis we found an immediate decrease of polymorphonuclear leukocytes in response to an increase of most gaseous and particulate pollutants. Lymphocytes increased within 24 hours in association with all gaseous pollutants but showed no effect in regard to particulate air pollution. Monocytes showed an increase associated with ultrafine particles, and nitrogen monoxide. The effect had two peaks in time, one 0-23 hours before blood withdrawal and a second one with a time lag of 48-71 hours. The increase of particulate and gaseous air pollution was associated with multiple changes in the differential white blood cell count in patients with chronic pulmonary diseases. PMID:20064088

  15. Comparison of Aryl Hydrocarbon Hydroxylase Induction in Cultured Blood Lymphocytes and Pulmonary Macrophages

    PubMed Central

    McLemore, Theodore L.; Martin, R. Russell; Toppell, Kenneth L.; Busbee, David L.; Cantrell, Elroy T.

    1977-01-01

    Aryl hydrocarbon hydroxylase induction was studied in cultured peripheral blood lymphocytes and pulmonary alveolar macrophages from 15 smokers and 8 nonsmokers with a variety of pulmonary diseases. Enzyme levels in lymphocytes from cigarette smokers cultured in medium without an inducing agent were 57±6 mU/106 cells (mean±SEM), while enzyme levels in lymphocytes from nonsmokers were 20±2 mU/106 cells (P < 0.001). When lymphocytes were cultured in the presence of the inducing agent, benzo-(a)anthracene, enzyme activity was increased to 168±23 mU/106 cells in smokers' cells and 99±22 mU/106 cells in lymphocytes from nonsmokers (P < 0.04). When noninduced enzyme values in cultured macrophages were compared, smokers' cells had enzyme levels of 45±5 mU/106 cells, whereas nonsmokers had enzyme activity of 24±2 mU/106 cells (P < 0.002). However, pulmonary macrophages from smokers or nonsmokers, cultured in the presence of benzo(a)-anthracene, had similar levels of induced enzyme activity (P > 0.1). A positive correlation was observed for nonsmokers (r = 0.596, P > 0.1 <0.2) or smokers (r = 0.640, P < 0.04), when enzyme values for noninduced cultures of macrophages and lymphocytes from individual patients were simultaneously compared. Enzyme values for macrophages and lymphocytes cultured in the presence of an inducer also revealed a positive correlation for individual smokers (r = 0.801, P < 0.001) or nonsmokers (r = 0.785, P < 0.01). Inducibility (expressed as fold-induction) for macrophages and lymphocytes from individual patients was also positively correlated (r = 0.889, P < 0.001 for nonsmokers and r = 0.942, P < 0.001 for smokers). These results indicate that the capacity for aryl hydrocarbon hydroxylase induction is similar whether tested in lymphocytes or pulmonary macrophages from this group of pulmonary disease patients. PMID:908748

  16. Immunological characterization of bronchoalveolar lavage fluid in patients with acute pulmonary coccidioidomycosis.

    PubMed

    Nesbit, Lance A; Knox, Kenneth S; Nguyen, Chinh T; Roesch, Justin; Wheat, L Joseph; Johnson, Suzanne M; Pappagianis, Demosthenes; Chavez, Suzette; Ampel, Neil M

    2013-09-01

    The specific cellular immunological characteristics of bronchoalveolar lavage (BAL) fluid in acute pulmonary coccidioidomycosis have not been defined. BAL fluid from patients living in a coccidioidomycosis-endemic region of Arizona who were undergoing bronchoscopy because of pulmonary infiltrates was analyzed. Mononuclear cells from BAL fluid and peripheral blood mononuclear cells (PBMCs) were incubated with the coccidioidal antigen T27K in vitro, and cellular immunological assays were performed. Forty-six patients were studied. Twelve received a diagnosis of acute pulmonary coccidioidomycosis, 17 received other diagnoses, and 17 had no diagnosis established. There was an increased proportion of polyfunctional CD8(+) T cells after antigen stimulation from subjects with coccidioidomycosis as compared to those with another diagnosis (P = .025). In cells collected from BAL fluid and in PBMCs, the concentrations of interferon γ, tumor necrosis factor α, and interleukin 17 (IL-17) were all significantly increased in samples from those with acute pulmonary coccidioidomycosis, compared with the other 2 groups (for all, P<.05). When incubated in vitro with a coccidioidal antigen preparation, cells from both BAL fluid and peripheral blood obtained from patients with pulmonary coccidioidomycosis demonstrated specific cellular immune responses, including expression of IL-17.

  17. Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial.

    PubMed

    Roche, Nicolas; Chapman, Kenneth R; Vogelmeier, Claus F; Herth, Felix J F; Thach, Chau; Fogel, Robert; Olsson, Petter; Patalano, Francesco; Banerji, Donald; Wedzicha, Jadwiga A

    2017-05-01

    Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β2-agonist combination versus a long-acting β2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups. Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with

  18. Nitric oxide modulation of pulmonary vascular resistance is red blood cell dependent in isolated rat lungs.

    PubMed

    Uncles, D R; Daugherty, M O; Frank, D U; Roos, C M; Rich, G F

    1996-12-01

    Nitric oxide (NO) or endothelium-derived relaxing factor may play an important role in modulating pulmonary vascular resistance (PVR), although previous studies have produced conflicting results. Endogenous NO inhibition causes an increase in PVR in intact animals but not in saline-perfused isolated lungs. We hypothesized that blood is essential for NO to serve as a modulator of PVR. Therefore, the effects of endogenous NO inhibition (N omega-nitro-L-arginine methyl ester [L-NAME]) were determined in isolated rat lungs as related to the presence of different blood components under normoxic conditions and after 1 wk of hypoxia (fraction of inspired oxygen [FIO2] = 10%). Exogenously administered inhaled NO was evaluated in isolated lungs from normoxic and hypoxic rats. In normoxic rats, L-NAME (10-100 microM) caused a dose-dependent increase in PVR in whole (hematocrit [Hct] 40%) and diluted (Hct 12%) blood-perfused lungs. L-NAME (10-800 microM) had no effect in isolated lungs perfused with a modified salt solution of equal viscosity to blood either alone, or containing plasma (50%) or free oxyhemoglobin (10 microM). In whole blood perfused lungs, L-NAME (100 microM) increased PVR more in hypoxic versus normoxic isolated lungs (141% vs 100%). Inhaled NO decreased PVR in isolated lungs from hypoxic rats and partially reversed the effects of L-NAME, but had no effect in normoxic lungs. In conclusion, endogenous and inhaled NO modulate PVR in isolated rat lungs and this role is increased by prolonged hypoxia. The response to inhibition of endogenous NO is dependent on the presence of red blood cells and is independent of the changes in viscosity or the presence of oxyhemoglobin or plasma.

  19. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

    PubMed Central

    Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

    2017-01-01

    Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

  20. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV.

    PubMed

    Triplette, Matthew; Attia, Engi F; Akgün, Kathleen M; Soo Hoo, Guy W; Freiberg, Matthew S; Butt, Adeel A; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T; Graber, Christopher J; Huang, Laurence; Crothers, Kristina

    2017-01-01

    The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1-39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

  1. Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

    PubMed

    Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; te Pas, Arjan B; Fouras, Andreas; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

    2016-03-01

    Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase.

  2. Peripheral arterial blood pressure versus central crterial blood pressure monitoring in critically ill patients after Cardio-pulmonary Bypass.

    PubMed

    Ahmad, Rana Altaf; Ahmad, Suhail; Naveed, Anjum; Baig, Mirza Ahmad Raza

    2017-01-01

    To determine the accuracy of peripheral (radial) arterial access as compared to central (femoral) arterial access for measurement of invasive blood pressure (IBP) in critically ill patients after cardiopulmonary bypass. Sixty patients (60) who required high inotropic/vasopressor support on weaning from cardio-pulmonary bypass and weaned off in 2(nd) attempt were included in this study. The duration of this study was from June 2015 to August 2016. Radial and femoral arterial access was achieved in all patients for simultaneous measurement of blood pressure. Arterial pressures were noted after 5, 15 and 30 minutes of weaning from cardiopulmonary bypass for both radial and femoral artery simultaneously. Mean age of study patients was 56.48±11.17 years. 85% patients were male. There was significant difference in systolic blood pressure, diastolic blood pressure and mean arterial pressures between the radial artery and femoral artery cannulation. Mean arterial pressures were significantly high in femoral artery as compared to the radial artery. The mean arterial pressures after five minutes of weaning using central access were 76.28±10.21 mmHg versus 64.15±6.76 mmHg in peripheral arterial access (p-value <0.001). Similarly we also found significant difference in mean arterial pressures after 15 minutes of weaning from cardiopulmonary bypass 78.70±10.12 mmHg in central access versus 72.03±6.76 mmHg using peripheral arterial access (p-value <0.001). The difference in arterial pressures were less marked as compared to the previous differences after 30 minutes of weaning from cardiopulmonary bypass as compared to the earlier readings (p-value 0.001). Peripheral arterial pressures are unreliable in critically ill patients after cardiopulmonary bypass receiving high dose of inotropic drugs. Central arterial access should be used in these patients to get accurate estimates of patients' blood pressure in early periods after cardiopulmonary bypass.

  3. In vivo support for the new concept of pulmonary blood flow-mediated CO2 gas excretion in the lungs.

    PubMed

    Kawai, Yoshiko; Ajima, Kumiko; Kaidoh, Maki; Sakaguchi, Masao; Tanaka, Satoshi; Kawamata, Mikito; Kimura, Hiroko; Ohhashi, Toshio

    2015-06-15

    To further examine the validity of the proposed concept of pulmonary blood flow-dependent CO2 gas excretion in the lungs, we investigated the effects of intramediastinal balloon catheterization-, pulmonary artery catheterization-, or isoprenaline (ISP)-induced changes in pulmonary blood flow on the end-expiratory CO2 gas pressure (PeCO2 ), the maximal velocity of the pulmonary artery (Max Vp), systemic arterial pressure, and heart rate of anesthetized rabbits. We also evaluated the changes in the PeCO2 in clinical models of anemia or pulmonary embolism. An almost linear relationship was detected between the PeCO2 and Max Vp. In an experiment in which small pulmonary arteries were subjected to stenosis, the PeCO2 fell rapidly, and the speed of the reduction was dependent on the degree of stenosis. ISP produced significant increases in the PeCO2 of the anesthetized rabbits. Conversely, treatment with piceatannol or acetazolamide induced significant reductions in the PeCO2 . Treatment with a cell surface F1/FO ATP synthase antibody caused significant reductions in the PeCO2 itself and the ISP-induced increase in the PeCO2 . Neither the PeCO2 nor SAP was significantly influenced by marked anemia [%hematocrit (Ht), 70 ∼ 47%]. On the other hand, in the presence of less severe anemia (%Ht: 100 ∼ 70%) both the PeCO2 and SAP fell significantly when the rabbits' blood viscosity was decreased. The rabbits in which pulmonary embolisms were induced demonstrated significantly reduced PeCO2 values, which was compatible with the lowering of their Max Vp. In conclusion, we reaffirm the validity of the proposed concept of CO2 gas exchange in the lungs.

  4. L-Carnitine Preserves Endothelial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Sharma, Shruti; Aramburo, Angela; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Xoinis, Kon; Kalkan, Gohkan; Fratz, Sohrab; Fineman, Jeffrey R.; Black, Stephen M.

    2013-01-01

    Background In our model of congenital heart disease (CHD) with increased pulmonary blood flow (Shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased eNOS/Hsp90 interactions that contribute to eNOS uncoupling, increased superoxide levels, and decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that L-carnitine therapy would maintain mitochondrial function, and NO signaling. Methods Thirteen fetal lambs underwent in utero placement of an aortopulmonary graft. Immediately following delivery, lambs received daily treatment with oral L-carnitine or its vehicle. Results L-carnitine-treated lambs had decreased levels of acyl carnitine, and a reduced acyl carnitine: free carnitine ratio compared to vehicle treated Shunt lambs. These changes correlated with increased carnitine acetyl transferase (CrAT) protein and enzyme activity and decreased levels of nitrated CrAT. The lactate: pyruvate ratio was also decreased in L-carnitine-treated lambs. Hsp70 protein levels were significantly decreased and this correlated with increases in eNOS/Hsp90 interactions, NOS activity, NOx levels, and a significant decrease in eNOS-derived superoxide. Further, acetylcholine significantly decreased left pulmonary vascular resistance (PVR) only in L-carnitine-treated lambs. Conclusion L-carnitine therapy may improve the endothelial dysfunction noted in children with CHD, and has important clinical implications that warrant further investigation. PMID:23628882

  5. Characterization of optimal resting tension in human pulmonary arteries

    PubMed Central

    Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud

    2016-01-01

    AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938

  6. Red blood cell dynamics in biomimetic microfluidic networks of pulmonary alveolar capillaries

    PubMed Central

    Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

    2017-01-01

    The pulmonary capillary networks (PCNs) embody organ-specific microvasculatures, where blood vessels form dense meshes that maximize the surface area available for gas exchange in the lungs. With characteristic capillary lengths and diameters similar to the size of red blood cells (RBCs), seminal descriptions coined the term “sheet flow” nearly half a century ago to differentiate PCNs from the usual notion of Poiseuille flow in long straight tubes. Here, we revisit in true-scale experiments the original “sheet flow” model and devise for the first time biomimetic microfluidic platforms of organ-specific PCN structures perfused with RBC suspensions at near-physiological hematocrit levels. By implementing RBC tracking velocimetry, our measurements reveal a wide range of heterogonous RBC pathways that coexist synchronously within the PCN; a phenomenon that persists across the broad range of pressure drops and capillary segment sizes investigated. Interestingly, in spite of the intrinsic complexity of the PCN structure and the heterogeneity in RBC dynamics observed at the microscale, the macroscale bulk flow rate versus pressure drop relationship retains its linearity, where the hydrodynamic resistance of the PCN is to a first order captured by the characteristic capillary segment size. To the best of our knowledge, our in vitro efforts constitute a first, yet significant, step in exploring systematically the transport dynamics of blood in morphologically inspired capillary networks. PMID:28090238

  7. Red blood cell dynamics in biomimetic microfluidic networks of pulmonary alveolar capillaries.

    PubMed

    Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

    2017-01-10

    The pulmonary capillary networks (PCNs) embody organ-specific microvasculatures, where blood vessels form dense meshes that maximize the surface area available for gas exchange in the lungs. With characteristic capillary lengths and diameters similar to the size of red blood cells (RBCs), seminal descriptions coined the term "sheet flow" nearly half a century ago to differentiate PCNs from the usual notion of Poiseuille flow in long straight tubes. Here, we revisit in true-scale experiments the original "sheet flow" model and devise for the first time biomimetic microfluidic platforms of organ-specific PCN structures perfused with RBC suspensions at near-physiological hematocrit levels. By implementing RBC tracking velocimetry, our measurements reveal a wide range of heterogonous RBC pathways that coexist synchronously within the PCN; a phenomenon that persists across the broad range of pressure drops and capillary segment sizes investigated. Interestingly, in spite of the intrinsic complexity of the PCN structure and the heterogeneity in RBC dynamics observed at the microscale, the macroscale bulk flow rate versus pressure drop relationship retains its linearity, where the hydrodynamic resistance of the PCN is to a first order captured by the characteristic capillary segment size. To the best of our knowledge, our in vitro efforts constitute a first, yet significant, step in exploring systematically the transport dynamics of blood in morphologically inspired capillary networks.

  8. Inhaled NO therapy increases blood nitrite, nitrate and S-nitrosohemoglobin concentrations in infants with pulmonary hypertension

    PubMed Central

    Ibrahim, Yomna I.; Ninnis, Janet R.; Hopper, Andrew O.; Deming, Douglas D.; Zhang, Amy X.; Herring, Jason L.; Sowers, Lawrence C.; McMahon, Timothy J.; Power, Gordon G.; Blood, Arlin B.

    2011-01-01

    Objective To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension. Study design In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12). Results After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change. Conclusion Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs. PMID:21907348

  9. Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

    PubMed

    Ibrahim, Yomna I; Ninnis, Janet R; Hopper, Andrew O; Deming, Douglas D; Zhang, Amy X; Herring, Jason L; Sowers, Lawrence C; McMahon, Timothy J; Power, Gordon G; Blood, Arlin B

    2012-02-01

    To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs. Copyright © 2012 Mosby, Inc. All rights reserved.

  10. Characterization of primary pulmonary adenosquamous carcinoma-associated pleural effusion.

    PubMed

    Stewart, Jennifer; Holloway, Andrew; Rasotto, Roberta; Bowlt, Kelly

    2016-03-01

    A 10-year-old, female spayed Shih Tzu was presented due to weight loss, increased respiratory effort and lethargy, determined to be secondary to a congenital para-esophageal diaphragmatic defect with partial herniation of the stomach and spleen. Four days following reduction surgery of the displaced abdominal organs thoracic effusion developed. Thoracic fluid evaluation revealed a cell-rich, protein-poor modified transudate with neutrophils, reactive mesothelial cells, and atypical epitheloid cells which occasionally appeared to be keratinizing, consistent with neoplastic exfoliation. Thoracic effusion recurred 2 days later, with similar characteristics as the initial sample. Computed tomography (CT) indicated consolidation and displacement of the right middle and accessory lung lobes. Exploratory thoracic surgery demonstrated a thickened, hyperemic right middle lung lobe, and thickened pericardial diaphragmatic ligament. Histologic evaluation of these tissues identified a primary pulmonary adenosquamous carcinoma with intravascular and pleural invasion. Based on these cytologic, histologic, and clinical findings, we conclude that primary pulmonary carcinomas may involve superficial thoracic structures and exfoliate into a thoracic effusion.

  11. MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis.

    PubMed

    Rosas, Ivan O; Richards, Thomas J; Konishi, Kazuhisa; Zhang, Yingze; Gibson, Kevin; Lokshin, Anna E; Lindell, Kathleen O; Cisneros, Jose; Macdonald, Sandra D; Pardo, Annie; Sciurba, Frank; Dauber, James; Selman, Moises; Gochuico, Bernadette R; Kaminski, Naftali

    2008-04-29

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression. We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins-MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A-that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%-100%) and specificity of 98.1% (95% CI 89.9%-100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%-100%) and specificity of 87.2% (95% CI 72.6%-95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%). Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases

  12. MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Konishi, Kazuhisa; Zhang, Yingze; Gibson, Kevin; Lokshin, Anna E; Lindell, Kathleen O; Cisneros, Jose; MacDonald, Sandra D; Pardo, Annie; Sciurba, Frank; Dauber, James; Selman, Moises; Gochuico, Bernadette R; Kaminski, Naftali

    2008-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression. Methods and Findings We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins—MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A—that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%–100%) and specificity of 98.1% (95% CI 89.9%–100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%–100%) and specificity of 87.2% (95% CI 72.6%–95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%). Conclusions Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung

  13. Postnatal episodic ozone results in persistent attenuation of pulmonary and peripheral blood responses to LPS challenge

    PubMed Central

    Maniar-Hew, Kinjal; Postlethwait, Edward M.; Fanucchi, Michelle V.; Ballinger, Carol A.; Evans, Michael J.; Harkema, Jack R.; Carey, Stephan A.; McDonald, Ruth J.; Bartolucci, Alfred A.

    2011-01-01

    Early life is a dynamic period of growth for the lung and immune system. We hypothesized that ambient ozone exposure during postnatal development can affect the innate immune response to other environmental challenges in a persistent fashion. To test this hypothesis, we exposed infant rhesus macaque monkeys to a regimen of 11 ozone cycles between 30 days and 6 mo of age; each cycle consisted of ozone for 5 days (0.5 parts per million at 8 h/day) followed by 9 days of filtered air. Animals were subsequently housed in filtered air conditions and challenged with a single dose of inhaled LPS at 1 yr of age. After completion of the ozone exposure regimen at 6 mo of age, total peripheral blood leukocyte and polymorphonuclear leukocyte (PMN) numbers were reduced, whereas eosinophil counts increased. In lavage, total cell numbers at 6 mo were not affected by ozone, however, there was a significant reduction in lymphocytes and increased eosinophils. Following an additional 6 mo of filtered air housing, only monocytes were increased in blood and lavage in previously exposed animals. In response to LPS challenge, animals with a prior history of ozone showed an attenuated peripheral blood and lavage PMN response compared with controls. In vitro stimulation of peripheral blood mononuclear cells with LPS resulted in reduced secretion of IL-6 and IL-8 protein in association with prior ozone exposure. Collectively, our findings suggest that ozone exposure during infancy can result in a persistent effect on both pulmonary and systemic innate immune responses later in life. PMID:21131396

  14. Modified Blalock-Taussig shunt versus ductal stenting for palliation of cardiac lesions with inadequate pulmonary blood flow.

    PubMed

    McMullan, David Michael; Permut, Lester Cal; Jones, Thomas Kenny; Johnston, Troy Alan; Rubio, Agustin Eduardo

    2014-01-01

    The modified Blalock-Taussig shunt is the most commonly used palliative procedure for infants with ductal-dependent pulmonary circulation. Recently, catheter-based stenting of the ductus arteriosus has been used by some centers to avoid surgical shunt placement. We evaluated the durability and safety of ductal stenting as an alternative to the modified Blalock-Taussig shunt. A single-institution, retrospective review of patients undergoing modified Blalock-Taussig shunt versus ductal stenting was performed. Survival, procedural complications, and freedom from reintervention were the primary outcome variables. A total of 42 shunted and 13 stented patients with similar age and weight were identified. Survival to second-stage palliation, definitive repair, or 12 months was similar between the 2 groups (88% vs 85%; P = .742). The incidence of surgical or catheter-based reintervention to maintain adequate pulmonary blood flow was 26% in the shunted patients and 25% in the stented patients (P = 1.000). Three shunted patients (7%) required intervention to address contralateral pulmonary artery stenosis and 3 (7%) required surgical reintervention to address nonpulmonary blood flow-related complications. The need for ipsilateral or juxtaductal pulmonary artery intervention at, or subsequent to, second-stage palliation or definitive repair was similar between the 2 groups. Freedom from reintervention to maintain adequate pulmonary blood flow was similar between infants undergoing modified Blalock-Taussig shunt or ductal stenting as an initial palliative procedure. However, a greater percentage of shunted patients experienced procedure-related complications and distal branch pulmonary artery stenosis. Palliative ductal stenting appears to be a safe and effective alternative to modified Blalock-Taussig in selected infants. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  15. Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

    NASA Technical Reports Server (NTRS)

    Mann, C. M.; Domino, K. B.; Walther, S. M.; Glenny, R. W.; Polissar, N. L.; Hlastala, M. P.

    1998-01-01

    We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain approximately 1,500 small pieces of lung ( approximately 1.7 cm3). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

  16. Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

    NASA Technical Reports Server (NTRS)

    Mann, C. M.; Domino, K. B.; Walther, S. M.; Glenny, R. W.; Polissar, N. L.; Hlastala, M. P.

    1998-01-01

    We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain approximately 1,500 small pieces of lung ( approximately 1.7 cm3). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

  17. Very Small Embryonic-like Stem Cells Are Mobilized in Human Peripheral Blood during Hypoxemic COPD Exacerbations and Pulmonary Hypertension.

    PubMed

    Guerin, Coralie L; Blandinières, Adeline; Planquette, Benjamin; Silvestre, Jean-Sébastien; Israel-Biet, Dominique; Sanchez, Olivier; Smadja, David M

    2017-03-11

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells involved in vascular and tissue regeneration and constitute a recruitable pool of stem/progenitor cells with putative instrumental role in organ repair. Here, we hypothesized that VSELs might be mobilized from the bone marrow (BM) to peripheral blood (PB) in patients with hypoxic lung disease or pulmonary hypertension (PH). The objective of the present study was then to investigate the changes in VSELs number in peripheral blood of patients with hypoxic lung disease and PH. We enrolled 26 patients with Chronic Obstructive Pulmonary Disease (COPD) with or without hypoxemia, 13 patients with PH and 20 controls without any respiratory or cardiovascular diseases. In PH patients, VSELs levels have been determined during right heart catheterization in pulmonary blood and PB. For this purpose, mononuclear cells were separated by density gradient and VSELs have been quantified by using a multiparametric flow cytometry approach. The number of PB-VSELs in hypoxic COPD patients was significantly increased compared with non-hypoxic COPD patients or controls (p = 0.0055). In patients with PH, we did not find any difference in VSELs numbers between arterial pulmonary blood and venous PB (p = 0.93). However, we found an increase in VSELs in the peripheral blood of patients with PH (p = 0.03). In conclusion, we unraveled that circulating VSELs were increased in peripheral blood of patients with hypoxic COPD or with PH. Thus, VSELs may serve as a reservoir of pluripotent stem cells that can be recruited into PB and may play an important role in promoting lung repair.

  18. Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages.

    PubMed

    Frellstedt, Linda; Waldschmidt, Ingrid; Gosset, Philippe; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Farnir, Frédéric; Franck, Thierry; Dupuis-Tricaud, Marie-Capucine; Lekeux, Pierre; Art, Tatiana

    2014-07-01

    In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, intensively trained, and deconditioned states before and after a strenuous exercise test. The cells were analyzed for TLR messenger ribonucleic acid (mRNA) expression by real-time PCR in vitro, and cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with LPS and a synthetic diacylated lipoprotein showed increased cytokine secretion in trained and deconditioned subjects, indicating the activation of cells at the systemic level. The production of TNF-α and IFN-β in nonstimulated and stimulated PAMs was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection.

  19. Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

    PubMed Central

    Benito, Natividad; Moreno, Asunción; Filella, Xavier; Miró, José M.; González, Julià; Pumarola, Tomás; Valls, María Eugenia; Luna, Montserrat; García, Felipe; Rañó, Ana; Torres, Antoni; Gatell, José M.

    2004-01-01

    We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5). PMID:15138189

  20. Red Blood Cell Distribution Width in Patients With Chronic Obstructive Pulmonary Disease and Healthy Subjects.

    PubMed

    Ozgul, Guler; Seyhan, Ekrem Cengiz; Özgül, Mehmet Akif; Günlüoğlu, Mehmet Zeki

    2017-03-01

    Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease (CVD). Red blood cell distribution width (RDW) is accepted as a powerful predictor of outcomes in patients with CVD. To study RDW in patients with COPD, and to compare the value of this measurement with clinical, echocardiographic, nutritional and laboratory status. Secondly, we aimed to determine the effect of smoking on RDW values in healthy subjects. One hundred and seventy-five patients with stable COPD and 210 healthy controls were enrolled in the study. Demographic, clinical, nutritional status, echocardiographic, and laboratory characteristics, RDW values were recorded and compared. RDW values were higher in the COPD group than in controls (15±2.3% vs. 13.8±2.5%, p<0.001). In COPD patients, RDW levels positively correlated with CRP levels (r=0.27, P<.001), albumin levels (r=0.23, P=.04), right ventricular dysfunction (RVD) (r=0.24, P=.001), pulmonary hypertension (PAH) (r=0.1, P=.02), and presence of CVD (r=0.24, P=.02). In multivariable logistic regression suggested that presence of CVD (4.3; 95% CI: 1.3 to 11; P=.01), and presence of RVD (3.1; 95% CI: 1.7 to 8.3; P=.02) were independently related to elevated RDW levels in COPD patients. In the healthy population, correlations analysis showed only a significant correlation between RDW and cigarette smoking years (r=0.57, P<.001). RDW is independently associated with CVD and RVD in patients with COPD. In the healthy population, RDW is also associated with smoking status. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease

    PubMed Central

    Rossman, Matthew J.; Trinity, Joel D.; Garten, Ryan S.; Ives, Stephen J.; Conklin, Jamie D.; Barrett-O'Keefe, Zachary; Witman, Melissa A. H.; Bledsoe, Amber D.; Morgan, David E.; Runnels, Sean; Reese, Van R.; Zhao, Jia; Amann, Markus; Wray, D. Walter

    2015-01-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population. PMID:26188020

  2. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

    PubMed

    Rossman, Matthew J; Trinity, Joel D; Garten, Ryan S; Ives, Stephen J; Conklin, Jamie D; Barrett-O'Keefe, Zachary; Witman, Melissa A H; Bledsoe, Amber D; Morgan, David E; Runnels, Sean; Reese, Van R; Zhao, Jia; Amann, Markus; Wray, D Walter; Richardson, Russell S

    2015-09-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.

  3. Characterization of a postlavage, in situ pulmonary macrophage population.

    PubMed

    Drath, D B; Davies, P; Shorey, J M; Gibran, N S; Simpson, P J; Huber, G L

    1982-04-01

    A postlavage in situ subpopulation of pulmonary macrophages (PM), biochemically distinct from the lavaged population, has recently been isolated from rats. After exhaustive bronchopulmonary lavage to extract the free lung cells, the lungs were excised, homogenized, and filtered, and the resultant cell suspension was allowed to form a monolayer on plastic Petri dishes. Electron microscopic morphometry failed to indicate any morphologic differences in the two populations. The postlavage in situ PM were more active metabolically during phagocytosis of zymosan particles or stimulation by phorbol myristate acetate (PMA) than the corresponding lavage population, as evidenced by greater superoxide generation. Macrophages prepared by either method became more avidly phagocytic when incubated with cell-free medium isolated in the preparation of the situ population. Peroxidase, an enzyme absent from the granules of PM separated by lavage techniques, was found in a granule-rich fraction of the in situ macrophage. Catalase activity was found in similar amounts in both supernatants and granule-rich fractions of both populations. The results support the concept of subpopulations of PM and suggest that these subpopulations are distinguished by their biochemical properties and their functional abilities.

  4. Characterization of the human blood plasma proteome

    SciTech Connect

    Shen, Yufeng; Kim, Jeongkwon; Strittmatter, Eric F.; Jacobs, Jon M.; Camp, David G.; Fang, Ruihua; Tolic, Nikola; Moore, Ronald J.; Smith, Richard D.

    2005-10-15

    We describe methods for broad characterization of the human plasma proteome. The combination of stepwise IgG and albumin protein depletion by affinity chromatography and ultrahigh-efficiency capillary liquid chromatography separations coupled to ion trap-tandem mass spectrometry enabled identification of 2392 proteins from a single plasma sample with an estimated confidence level of >94%, and an additional 2198 proteins with an estimated confidence level of 80%. The relative abundances of the identified proteins span a range of over eight orders of magnitude in concentration (<30 pg/mL to {approx}30 mg/mL), facilitated by the attomole-level sensitivity of the analysis methods. More than 80% of the observed proteins demonstrate interactions with IgG and/or albumin. The results from this study provide a basis for a wide range of plasma proteomics studies, including broad quantitation of relative abundances in comparative studies for the identification of novel protein disease markers, as well as further studies of protein-protein interactions.

  5. Further characterization of computed tomographic and clinical features for staging and prognosis of idiopathic pulmonary fibrosis in West Highland white terriers.

    PubMed

    Thierry, Florence; Handel, Ian; Hammond, Gawain; King, Lesley G; Corcoran, Brendan M; Schwarz, Tobias

    2017-07-01

    Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (ρ = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (ρ = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P < 0.001). The most common CT characteristics were ground-glass pattern (16/21) considered as a mild degree of severity, and focal reticular and mosaic ground-glass patterns (10/21) considered as a moderate degree of severity. Findings supported the use of thoracic CT as a method for characterizing idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. © 2017 The Authors

  6. Characterization of pulmonary sigma receptors by radioligand binding

    PubMed Central

    Lever, John R.; Litton, Tyler P.; Fergason-Cantrell, Emily A.

    2015-01-01

    This study establishes the expression of appreciable populations of sites on mouse lung membranes that exhibit radioligand binding properties and pharmacology consistent with assignment as sigma1 and sigma2 receptors. Specific binding of the sigma1 receptor radioligand [3H](+)-pentazocine reached steady state within 6 h at 37 °C. Saturation studies revealed high affinity binding to a single class of sites (Kd 1.36 ± 0.04 nM; Bmax 967 ± 11 fmol / mg protein). Inhibition studies showed appropriate sigma1 receptor pharmacology, including higher affinity for (+)-N-allylnormetazocine with respect to the (−)-enantiomer, and positive allosteric modulation of dextromethorphan binding by phenytoin. Using [3H]1,3-di(2-tolyl)guanidine in the presence of (+)-pentazocine to assess sigma2 receptor binding, steady state was achieved within 2 min at 25 °C. Cold saturation studies revealed one high affinity, low capacity binding site (Kd 31.8 ± 8.3 nM; Bmax 921 ± 228 fmol / mg protein) that displayed sigma2 receptor pharmacology. A very low affinity, high capacity interaction also was observed that represents saturable, but not sigma receptor specific, binding. A panel of ligands showed rank order inhibition of radioligand binding appropriate for the sigma2 receptor, with ifenprodil displaying the highest apparent affinity. In vivo, dextromethorphan inhibited the specific binding of a radioiodinated sigma1 receptor ligand in lung with an ED50 of 1.2 µmol / kg, a value near the recommended dosage for the drug as a cough suppressant. Overall, the present work provides a foundation for studies of drug interactions with pulmonary sigma1 and sigma2 receptors in vitro and in vivo. PMID:26004528

  7. Role of Rho-kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension.

    PubMed

    Schwenke, Daryl O; Pearson, James T; Sonobe, Takashi; Ishibashi-Ueda, Hatsue; Shimouchi, Akito; Kangawa, Kenji; Umetani, Keiji; Shirai, Mikiyasu

    2011-04-01

    Rho-kinase-mediated vasoconstriction and endothelial dysfunction are considered two primary instigators of pulmonary arterial hypertension (PAH). However, their contribution to the adverse changes in pulmonary blood flow distribution associated with PAH has not been addressed. This study utilizes synchrotron radiation microangiography to assess the specific role, and contribution of, Rho-kinase-mediated vasoconstriction and endothelial dysfunction in PAH. Male adult Sprague-Dawley rats were injected with saline (Cont-rats) or monocrotaline (MCT-rats) 3 wk before microangiography was performed on the left lung. We assessed dynamic changes in vessel internal diameter (ID) in response to 1) the Rho-kinase inhibitor fasudil (10 mg/kg iv); or 2) ACh (3 μg · kg⁻¹ · min⁻¹), sodium nitroprusside (SNP, 5 μg · kg⁻¹ · min⁻¹), and N(ω)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg iv). We observed that MCT-rats had fewer vessels of the microcirculation compared with Cont-rats. The fundamental result of this study is that fasudil improved pulmonary blood flow distribution and reduced pulmonary pressure in PAH rats, not only by dilating already-perfused vessels (ID > 100 μm), but also by restoring blood flow to vessels that had previously been constricted closed (ID < 100 μm). Endothelium-dependent vasodilation was impaired in MCT-rats primarily in vessels with an ID < 200 μm. Moreover the vasoconstrictor response to l-NAME was accentuated in MCT-rats, but only in the 200- to 300-μm vessels. These results highlight the importance of Rho-kinase-mediated control and endothelial control of pulmonary vascular tone in PAH. Indeed, an effective therapeutic strategy for treating PAH should target both the smooth muscle Rho-kinase and endothelial pathways.

  8. Pulmonary blood volume measured by contrast enhanced ultrasound: a comparison with transpulmonary thermodilution.

    PubMed

    Herold, I H F; Soliman Hamad, M A; van Assen, H C; Bouwman, R A; Korsten, H H M; Mischi, M

    2015-07-01

    Blood volume quantification is essential for haemodynamic evaluation guiding fluid management in anaesthesia and intensive care practice. Ultrasound contrast agent (UCA)-dilution measured by contrast enhanced ultrasound (CEUS) can provide the UCA mean transit time (MTT) between the right and left heart, enabling the assessment of the intrathoracic blood volume (ITBV(UCA)). The purpose of the present study was to investigate the agreement between UCA-dilution using CEUS and transpulmonary thermodilution (TPTD) in vitro and in vivo. In an in vitro setup, with variable flows and volumes, we injected a double indicator, ice-cold saline with SonoVue(®), and performed volume measurements using transesophageal echo and thermodilution by PiCCO(®). In a pilot study, we assigned 17 patients undergoing elective cardiac surgery for pulmonary blood volume (PBV) measurement using TPTD by PiCCO(®) and ITBV by UCA-dilution. Correlation coefficients and Bland-Altman analysis were performed for all volume measurements. In vitro, 73 experimental MTT's were obtained using PiCCO(®) and UCA-dilution. The volumes by PiCCO(®) and UCA-dilution correlated with true volumes; r(s)=0.96 (95% CI, 0.93-0.97; P<0.0001) and r(s)=0.97 (95% CI, 0.95-0.98; P<0.0001), respectively. The bias of PBV by PiCCO(®) and ITBV(UCA) were -380 ml and -42 ml, respectively. In 16 patients, 86 measurements were performed. The correlation between PBV by PiCCO(®) and ITBV(UCA) was r(s)=0.69 (95% CI 0.55-0.79; P<0.0001). Bland-Altman analysis revealed a bias of -323 ml. ITBV assessment with CEUS seems a promising technique for blood volume measurement, which is minimally-invasive and bedside applicable. ISRCTN90330260. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

    PubMed Central

    Korossis, Sotirios A.; Wilshaw, Stacy-Paul; Jennings, Louise M; Fisher, John; Ingham, Eileen

    2014-01-01

    Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure. PMID:24786313

  10. [Partial anomalous pulmonary venous connection as incidental finding: Explanation for apparently paradoxical central venous blood gas analysis results].

    PubMed

    Brandt, L; Artmeier-Brandt, U

    2015-10-01

    A partial anomalous pulmonary venous connection (PAPVC) is a congenital abnormality of the great thoracic vessels the incidence of which is underestimated and is associated with a left-right shunt. It rarely develops into a right-sided cardiac insufficiency. Because of the mostly low left-right shunt volume, a PAPVC is often asymptomatic and mostly incidentally detected in advanced age. Incorrect positioning of a central venous catheter or paradoxical blood gas parameters can serve to indicate the presence of a PAPVC. This article presents the case a 50-year-old patient with a PAPVC of the left upper lobe pulmonary vein draining into the left innominate vein without prior clinical symptoms. Blood gas analyses from the superior vena cava, where the catheter placement was confirmed by computed tomography angiography, showed unexplainable arterial values. The anatomical abnormality was confirmed by computed tomography.

  11. Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome

    PubMed Central

    Maissen-Villiger, Carla A.; Schweighauser, Ariane; van Dorland, H. Anette; Morel, Claudine; Bruckmaier, Rupert M.; Zurbriggen, Andreas; Francey, Thierry

    2016-01-01

    Background Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. Methodology and Principal Findings The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. Conclusion The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance

  12. Assessment of regional pulmonary blood flow using (68)Ga-DOTA PET.

    PubMed

    Velasco, Carlos; Mateo, Jesus; Santos, Arnoldo; Mota-Cobian, Adriana; Herranz, Fernando; Pellico, Juan; Mota, Ruben A; España, Samuel; Ruiz-Cabello, Jesus

    2017-12-01

    In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of (68)Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal. Each radiotracer injection was performed simultaneously to the injection of fluorescent microspheres. PBF images were generated applying a two-compartment exchange model over the dynamic PET images. PET and microspheres values were compared by regression analysis and Bland-Altman plot. The capability of the proposed technique to produce 3D regional PBF images was demonstrated. The correlation evaluation between (68)Ga-DOTA PET and microspheres showed a good and significant correlation (r = 0.74, P < 0.001). Assessment of PBF with the proposed technique allows combining the high quantitative accuracy of PET imaging with the use of (68)Ga/(68)Ge generators. Thus, (68)Ga-DOTA PET emerges as a potential inexpensive method for measuring PBF in clinical settings with an extended use.

  13. Documentation of impaired coronary blood flow in chronic obstructive pulmonary disease patients.

    PubMed

    Selcuk, Hatice; Maden, Orhan; Selcuk, Mehmet Timur; Celenk, Mehmet Kutlu; Geyik, Bilal; Tüfekcioglu, Omac

    2010-02-01

    In the current study, the effects of moderate to severe chronic obstructive pulmonary disease (COPD) on coronary blood flow in patients with angiographically proven normal coronary arteries was evaluated. A total of 85 patients with moderate to severe COPD and 39 age- and sex-matched control partcipants, who underwent diagnostic coronary angiography and found to have normal epicardial coronary angiogram constituted the COPD and control groups, respectively. The 2 groups were compared for Thrombolysis In Myocardial Infarction (TIMI) frame counts in each major coronary artery. The TIMI frame count of the COPD group was significantly higher than that of control group for all 3 major individual coronary arteries: left anterior descending (corrected), 37+/-13 vs 20+/-4; right coronary artery, 32+/-14 vs 21+/-4; and left circumflex artery, 34+/-12 vs 20+/-5, (P<0.001 for all). In addition, TIMI frame counts in individual coronary arteries were found to be positively correlated with forced expiratory volume 1 s percent, serum high sensitive C-reactive protein and fibrinogen concentrations, in the COPD group. Our findings suggest that an increased slow coronary flow might be a manifestation of harmful effects of COPD on the coronary circulation, regardless of the underlying mechanism.

  14. Morphometry of the extremely thin pulmonary blood-gas barrier in the chicken lung.

    PubMed

    Watson, Rebecca R; Fu, Zhenxing; West, John B

    2007-03-01

    The gas exchanging region in the avian lung, although proportionally smaller than that of the mammalian lung, efficiently manages respiration to meet the high energetic requirements of flapping flight. Gas exchange in the bird lung is enhanced, in part, by an extremely thin blood-gas barrier (BGB). We measured the arithmetic mean thickness of the different components (endothelium, interstitium, and epithelium) of the BGB in the domestic chicken lung and compared the results with three mammals. Morphometric analysis showed that the total BGB of the chicken lung was significantly thinner than that of the rabbit, dog, and horse (54, 66, and 70% thinner, respectively) and that all layers of the BGB were significantly thinner in the chicken compared with the mammals. The interstitial layer was strikingly thin in the chicken lung ( approximately 86% thinner than the dog and horse, and 75% thinner than rabbit) which is a paradox because the strength of the BGB is believed to come from the interstitium. In addition, the thickness of the interstitium was remarkably uniform, unlike the mammalian interstitium. The uniformity of the interstitial layer in the chicken is attributable to a lack of the supportive type I collagen cable that is found in mammalian alveolar lungs. We propose that the surrounding air capillaries provide additional structural support for the pulmonary capillaries in the bird lung, thus allowing the barrier to be both very thin and extremely uniform. The net result is to improve gas exchanging efficiency.

  15. Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

    PubMed

    Hirata, Yoshinori; Sata, Makoto; Makiuchi, Yuko; Morikane, Keita; Wada, Akihito; Okabe, Nobuhiko; Tomoike, Hitonobu

    2009-12-01

    During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

  16. [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

    PubMed

    Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

  17. Endogenous endothelium-derived relaxing factor opposes hypoxic pulmonary vasoconstriction and supports blood flow to hypoxic alveoli in anesthetized rabbits.

    PubMed Central

    Sprague, R S; Thiemermann, C; Vane, J R

    1992-01-01

    Agents that inhibit nitric oxide synthesis augment hypoxic pulmonary vasoconstriction. In an animal model of unilateral alveolar hypoxia, we investigated the hypothesis that endogenous endothelium-derived relaxing factor/nitric oxide opposes hypoxic pulmonary vasoconstriction and supports blood flow to hypoxic alveoli, resulting in a reduction in arterial oxygen tension (PO2). In pentobarbital-anesthetized rabbits, unilateral alveolar hypoxia was produced by ventilation of one lung with 100% oxygen and the other with 100% nitrogen (O2/N2). NG-Nitro-L-arginine methyl ester (0.03 followed by 1.0 mg/kg i.v.) resulted in dose-dependent decreases in the percent of pulmonary blood flow to the N2-ventilated lung and increases in arterial PO2. L-Arginine (1 mg.kg-1.min-1 i.v.) prevented the NG-nitro-L-arginine methyl ester-induced redistribution of blood flow away from hypoxic alveoli and improvement in arterial PO2. Indomethacin (5 mg/kg i.v.) administered during O2/N2 ventilation resulted in a reduction in the percentage of total blood flow to the hypoxic lung and an increase in arterial PO2. However, NG-nitro-L-arginine methyl ester administered in the presence of indomethacin caused additional diversion of blood flow away from the hypoxic lung. The magnitude of the changes suggests that the endothelium-derived relaxing factor/nitric oxide system has the capacity to make a greater contribution than products of cyclooxygenase-mediated arachidonic acid metabolism in supporting blood flow to hypoxic alveoli in the rabbit. Images PMID:1528883

  18. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  19. [Lung pathology of complex congenital heart defect with diminished pulmonary blood flow but without aortopulmonary collateral artery and patent ductus arteriosus in infants and young children].

    PubMed

    Zhang, Xiao-Tong; Liu, Ying-Long; Ruan, Ying-Mao; Yu, Cun-Tao; Liu, Lei

    2008-06-01

    The development of pulmonary vascular bed is strongly flow-dependent. Abnormal pulmonary blood flow leads to pulmonary pathological changes. This study aimed to observe the pathological changes of small pulmonary arteries and alveoli in complex congenital heart defect with diminished pulmonary blood flow but without aortopulmonary collateral artery (APCA) and patent ductus arteriosus (PDA) in infants and young children. Autopsy pulmonary specimens obtained from 5 children who died of non-cardiovascular diseases were used as the control group (age: 4-18 months). Fifty-six children (age: 4-36 months) with complex congenital heart defect with diminished pulmonary blood flow but without APCA and PDA served as the study group, including 34 cases of tetralogy of Fallot, 7 cases of double outlet right ventricle with pulmonary stenosis, 9 cases of single ventricle with pulmonary stenosis, 4 cases of tricuspid atresia with pulmonary stenosis and 2 cases of complete atrioventricular septal defect with pulmonary stenosis. Pulmonary specimen sections were stained by hematoxylin-eosin and Weigert-Van Gieson. Percentage of media thickness (MT%), percentage of media section area (MS%), number of small arterial per square centimeter (APSC), mean alveolar number (MAN), mean linear intercept (MLI), proportion of parenchyma area in total area (PPA%) and alveolar to small arterial ratio per unit area (AAR) were measured by morphologic quantitative analysis. MT% (10.93+/-2.87% vs 15.08+/-2.51%), MS% (18.97+/-5.56% vs 25.04+/-3.87%) and APSC (202.43+/-67.45 vs 441.69+/-65.29) decreased significantly in the study group compared with the control group (P<0.01). The internal diameter of small pulmonary artery (80.26+/-21.57 microm vs 58.53+/-10.29 microm; P<0.05), AAR (46.59+/-14.43 vs 34.46+/-4.98; P<0.01) and MLI (144.98+/-44.87 microm vs 108.39+/-20.76 microm; P<0.05) increased significantly compared with the control group. The media of small pulmonary arteries becomes thinner, the

  20. Pulmonary Hemorrhage: Imaging with a New Magnetic Resonance Blood Pool Agent in Conjunction with Breathheld Three-Dimensional Magnetic Resonance Angiography

    SciTech Connect

    Weishaupt, Dominik; Hilfiker, Paul R.; Schmidt, Michaela; Debatin, Joerg F.

    1999-07-15

    Purpose: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. Methods: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30 deg.) were acquired breathheld over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. Results: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. Conclusion: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.

  1. Pharmacological characterization of histamine H3 receptors in isolated guinea pig pulmonary artery and ileum.

    PubMed

    Rizzo, C A; Tozzi, S; Monahan, M E; Hey, J A

    1995-12-27

    We characterized the histamine H3 receptors involved in the modulation of electrical field stimulated neurogenic contraction of guinea pig pulmonary artery sympathetic, and guinea pig ileum parasympathetic preparations. Simultaneous measures of electrical field stimulation-evoked 3H overflow and tension in [3H]norepinephrine-loaded pulmonary artery were sensitive to tetrodotoxin (300 nM) and insensitive to hexamethonium (100 microM). Only the contractile response was inhibited by prazosin (100 nM). (R)-alpha-Methylhistamine's inhibition of the pulmonary artery contraction and 3H overflow were dose-dependently antagonized by thioperamide (30-100 nM). (R)-alpha-Methylhistamine also inhibited the neurogenic contractions of the isolated ileum (pD2 = 8.2). In the pulmonary artery, the relative potency of the histamine H3 receptor antagonists vs. (R)-alpha-methylhistamine inhibition of neurogenic contractions (pD2 = 7.1) was thioperamide (pA2 = 8.6 +/- 0.1) > burimamide (pA2 = 7.6 +/- 0.2) > impromidine (pA2 = 6.9 +/- 0.02). Similarly, the relative potency of histamine H3 receptor antagonists in the isolated ileum was thioperamide > burimamide > or = impromidine, with pA2 estimates of 8.7 +/- 0.1, 7.3 +/- 0.1 and 7.1 +/- 0.1, respectively. Antagonist potencies suggest a predominant histamine H3A-like receptor population on postganglionic sympathetic neurons innervating the pulmonary artery and parasympathetic neurons innervating the ileum longitudinal muscle.

  2. 3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent.

    PubMed

    Fink, Christian; Ley, Sebastian; Puderbach, Michael; Plathow, Christian; Bock, Michael; Kauczor, Hans-Ulrich

    2004-07-01

    The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40 degrees; voxel size: 1.3 x 2.5 x 4.0 mm3; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40 degrees; voxel size: 0.8 x 1.0 x 1.6 mm3) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n = 2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21 +/- 8 vs. 13 +/- 3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.

  3. Central venous catheter-related blood stream infections in patients receiving intravenous iloprost for pulmonary hypertension.

    PubMed

    Sammut, D; Elliot, C A; Kiely, D G; Armstrong, I J; Martin, L; Wilkinson, J; Sephton, P; Jones, J; Hamilton, N; Hurdman, J; McLellan, E; Sabroe, I; Condliffe, R

    2013-07-01

    Catheter-related blood stream infection (CR-BSI) in patients with pulmonary hypertension (PH) receiving intravenous iloprost via an indwelling central line has previously not been fully described. Recent studies have suggested a link between the pH of prostanoid infusions and the rate and nature of CR-BSI. We have investigated CR-BSI in patients receiving intravenous iloprost at our unit. Databases and hospital records were interrogated for all patients receiving intravenous iloprost between September 2007 and June 2012. Fifty-nine patients received intravenous iloprost via an indwelling central catheter with a total of 23,072 treatment days. There were 15 episodes of CR-BSI, identified using a systematic screening protocol, involving 11 patients giving an overall CR-BSI rate of 0.65/1,000 treatment days. CR-BSI rate for Gram-positive organisms was 0.26/1,000 treatment-days and for Gram-negative organisms was 0.39/1,000 treatment-days. The pH of iloprost in typical dosing regimens was comparable to the pH used in standard-diluent treprostinil and dissimilar to alkaline epoprostenol infusions. The proportion of Gram-negative CR-BSI was similar to that reported for standard-diluent treprostinil. CRP was normal on admission in 33 % of cases of confirmed CR-BSI and remained normal in 13 % of cases. CR-BSI rates with intravenous iloprost are comparable to those observed for other prostanoids. The high proportion of Gram-negative organisms observed and the neutral pH of iloprost infusions support the previously hypothesised link between pH and antimicrobial activity. Although usually elevated during a CR-BSI, CRP may be normal in early infection and a normal result cannot completely exclude infection.

  4. Peripheral Blood Mononuclear Cell Gene Expression Profiles Predict Poor Outcome in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Herazo-Maya, Jose D.; Noth, Imre; Duncan, Steven R.; Kim, SungHwan; Ma, Shwu-Fan; Tseng, George C.; Feingold, Eleanor; Juan-Guardela, Brenda M.; Richards, Thomas J.; Lussier, Yves; Huang, Yong; Vij, Rekha; Lindell, Kathleen O.; Xue, Jianmin; Gibson, Kevin F.; Shapiro, Steven D.; Garcia, Joe G. N.; Kaminski, Naftali

    2014-01-01

    We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by performing microarray experiments of PBMCs in discovery and replication cohorts of IPF patients. Microarray analyses identified 52 genes associated with transplant-free survival (TFS) in the discovery cohort. Clustering the microarray samples of the replication cohort using the 52-gene outcome-predictive signature distinguished two patient groups with significant differences in TFS. We studied the pathways associated with TFS in each independent microarray cohort and identified decreased expression of “The costimulatory signal during T cell activation” Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and ITK, results confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR expression of CD28, ICOS, LCK, and ITK along with patient’s age, gender, and percent predicted forced vital capacity (FVC%), demonstrated an area under the receiver operating characteristic curve of 78.5% at 2.4 months for death and lung transplant prediction in the replication cohort. To evaluate the potential cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found significant correlation of these genes with the PBMC percentage of CD4+CD28+ T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and ITK are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies. PMID:24089408

  5. Vertical Distributions of Pulmonary Diffusing Capacity and Capillary Blood Flow in Man

    PubMed Central

    Michaelson, Edward D.; Sackner, Marvin A.; Johnson, Robert L.

    1973-01-01

    In six normal upright subjects, a 100 mol bolus—composed of equal parts of neon, carbon monoxide, and acetylene (Ne, CO, and C2H2)—was inspired from either residual volume (RV) or functional residual capacity (FRC) during a slow inspiration from RV to total lung capacity (TLC). After breath holding and subsequent collection of the exhalate, diffusing capacity and pulmonary capillary blood flow per liter of lung volume (DL/VA and Q̇C/VA) were calculated from the rates of CO and C2H2 disappearances relative to Ne. The means: DL/VA = 5.26 ml/min × mm Hg per liter (bolus at RV), 6.54 ml/min × mm Hg per liter (at FRC); Q̇C/VA 0.537 liters/minute per liter (bolus at RV), 0.992 liters/minute per liter (at FRC). Similar maneuvers using Xenon-133 confirmed that, during inspiration, more of the bolus goes to the upper zone if introduced at RV and more to the lower, if at FRC. A lung model has been constructed which describes how DL/VA and Q̇C/VA must be distributed to satisfy the experimental data. According to this model, there is a steep gradient of Q̇C/VA, increasing from apex to base, similar to that previously determined by other techniques—and also a gradient in the same direction, although not as steep, for DL/VA. This more uniform distribution of DL/VA compared with Q̇C/VA indicates a vertical unevenness of diffusing capacity with respect to blood flow (DL/Q̇C). However, the relative degree of vertical unevenness of DL/VA compared with Q̇C/VA can account only in part for previous observations attributed to the inhomogeneity of DL/VA and Q̇C/VA. Thus, a more generalized unevennes of these ratios must exist throughout the lung, independent of gravitation. Images PMID:4683876

  6. Increased Regulatory and Decreased CD8+ Cytotoxic T Cells in the Blood of Patients with Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Ulrich, Silvia; Nicolls, Mark R.; Taraseviciene, Laima; Speich, Rudolf; Voelkel, Norbert

    2008-01-01

    Background An association between pulmonary arterial hypertension (PAH) and various immune disorders is well established. Recently, the role of an intact immune system in protecting against pulmonary angioproliferation was shown in an animal model. Objective To elucidate the role of T cells in human PAH, we comparatively studied T cell subclasses with emphasis on regulatory T cells (Treg) in the peripheral blood of patients with idiopathic pulmonary arterial hypertension (IPAH) and healthy controls. Methods Isolated peripheral blood mononuclear cells from 36 patients diagnosed with IPAH and 33 healthy controls were stained with fluorescently labeled monoclonal antibodies against superficial T cell markers (CD3, CD4, CD8, CD25) and FoxP3, the intracellular marker of Treg cells. The relative cell distribution was analyzed by flow cytometry. The functionality of patient and control Treg cells was assessed by coculture of Treg with nonregulatory T cells from the same individual. Results Significantly less CD8+ T cells (p = 0.02) and more CD25hi+ and FoxP3+CD4+ T cells were found in the peripheral blood of patients compared with controls (p = 0.009 and p < 0.001, respectively). The percentage of FoxP3+ cells within the CD25hi+CD4+ Treg cells was similar. Treg cell functionality was equal in patients and controls. Conclusion Our findings of decreased CD8+ T cells and increased Treg cells in the peripheral blood of patients with IPAH are novel and may have implications for directing future research in the field to elucidate the differential role of T cells and the immune system in IPAH. PMID:18025812

  7. Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise.

    PubMed

    Huang, Y C; Helms, M J; MacIntyre, N R

    1994-02-01

    Previous approaches to the measurements of pulmonary diffusing capacity (DL) and pulmonary capillary blood flow (QC) utilized either the rebreathing or the single inhalation technique in conjunction with radioisotope gas and mass spectrometry. In the present study, we utilized a newly developed rapid infrared analyzer in conjunction with the slow single exhalation technique on 100 healthy volunteers to establish normal values for DL and QC under sitting, supine, and exercise conditions. The exercise level was determined by a target heart rate: HRex = ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age, sex, height, or weight were then computed for sitting, supine, and exercise values. We found that mean DL and QC increased by approximately 12 percent and 8 percent, respectively, from sitting to supine posture, and by approximately 30 percent and 100 percent, respectively, from sitting (rest) to mild exercise. These results provided a database for further studies in the single exhalation method in various clinical settings.

  8. Detection and Characterization of Carcinoma Cells in the Blood

    NASA Astrophysics Data System (ADS)

    Racila, Emilian; Euhus, David; Weiss, Arthur J.; Rao, Chandra; McConnell, John; Terstappen, Leon W. M. M.; Uhr, Jonathan W.

    1998-04-01

    A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45-, and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

  9. Characterization of intestinal collateral blood flow in the developing piglet.

    PubMed

    Crissinger, K D; Granger, D N

    1988-10-01

    Interest in the pathogenesis of neonatal necrotizing enterocolitis has prompted study of the intestinal circulation in developing animals. It is conceivable that poorly developed collateral channels may predispose the neonatal intestine to ischemic insults. We therefore characterized intestinal collateral blood flow in anesthetized and ventilated 1-day and 1-month-old piglets. Intestinal blood flow was measured with radioactive microspheres (15 micron diameter) before and after either 1) total occlusion of the superior mesenteric artery (SMA) or 2) occlusion of a distal (jejunoileal) branch of the SMA. After total SMA occlusion in 1-day and 1-month-old piglets, perfusion of the intestine via collaterals from the celiac and inferior mesenteric arteries was not evident. Jejunal, ileal, and colonic (except rectal) blood flows fell to zero 30 min after ligation of the SMA. Ligation of a distal branch of the SMA in 1-month-old animals significantly reduced total wall (by 25%) and mucosal/submucosal (by 25%) blood flows in the occluded segment. Similar experiments in 1-day-old piglets produced significantly greater reduction in total (70%) and mucosa/submucosa (70%) blood flows. Muscle/serosa blood flows in both groups were not significantly different from control values. In conclusion, collateral perfusion of the intestine via the celiac and inferior mesenteric arteries is insignificant during acute SMA occlusion in the developing piglet. Although there is significant collateral blood flow within the SMA vascular network, perfusion between adjacent gut segments is less effective in preventing intestinal ischemia after occlusion of a branch of the SMA in neonates than in 1-month-old piglets.

  10. Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) - Blood Clot Forming in a Vein

    MedlinePlus

    ... Clots Videos Quiz My Story Links to Other Websites Facts Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Deep Vein Thrombosis and Pulmonary Embolism (DVT/PE) are ...

  11. Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

    PubMed

    Levitzky, Michael G

    2006-03-01

    "Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

  12. Development of pulmonary blood flow evaluation method with a dynamic flat-panel detector: quantitative correlation analysis with findings on perfusion scan.

    PubMed

    Tanaka, Rie; Sanada, Shigeru; Fujimura, Masaki; Yasui, Masahide; Hayashi, Norio; Tsuji, Shiro; Okamoto, Hiroyuki; Nanbu, Yuko; Matsui, Osamu

    2010-01-01

    Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X-ray translucency, i.e., pixel values. Thus, decreased blood flow should be observed as a reduction of the variation of X-ray translucency. We performed the present study to investigate the feasibility of pulmonary blood flow evaluation with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14 subjects were obtained with a dynamic FPD system. The changes in pixel value in each local area were measured and mapped on the original image by use of a gray scale in which small and large changes were shown in white and black, respectively. The resulting images were compared to the findings in perfusion scans. The cross-correlation coefficients of the changes in pixel value and radioactivity counts in each local area were also computed. In all patients, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on the mapping image, and a correlation was observed between the distribution of changes in pixel value and those in radioactivity counts (0.7 pulmonary blood flow. The present method is potentially useful for evaluating pulmonary blood flow as an additional examination in conventional chest radiography.

  13. Prospective study of ABO blood type and the risk of pulmonary embolism in two large cohort studies.

    PubMed

    Wolpin, Brian M; Kabrhel, Christopher; Varraso, Raphaëlle; Kraft, Peter; Rimm, Eric B; Goldhaber, Samuel Z; Camargo, Carlos A; Fuchs, Charles S

    2010-11-01

    Prior studies have suggested an association of ABO blood type and the risk of venous thromboembolism; however, most studies were retrospective and lacked important covariates or validated endpoints. Moreover, risk estimates varied widely across studies. Therefore, we prospectively examined the association of blood type and the risk of incident pulmonary embolism (PE) in two large cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. During 1,010,378 person-years of follow-up among 77,025 women and 30,105 men, 499 participants developed PE. Compared to those with O-blood type, participants with non-O blood type had multivariable-adjusted hazard ratios (HR) of 1.86 (95% CI, 1.35-2.57) for idiopathic PE, 1.29 (95% CI, 1.03-1.62) for non-idiopathic PE, and 1.46 (95% CI, 1.22-1.76) for any PE. Hazard ratios were similar for participants with blood types A, B, and AB. Age-adjusted absolute rates of idiopathic PE over 10 years of follow-up differed by blood type: 0.11% for O, 0.20% for A, 0.19% for AB, and 0.21% for B. For idiopathic PE, the population attributable fraction was 33% for inheritance of non-O blood type. Among past and current smokers, participants with non-O vs. O-blood type had a HR for idiopathic PE of 2.56 (95% CI, 1.61-4.08). Among never smokers, the HR for idiopathic PE was 1.30 (95% CI, 0.82-2.05; P interaction=0.04). In two large, prospective cohorts, ABO blood type was significantly associated with the risk of idiopathic and non-idiopathic PE, with even greater risk for idiopathic PE among current and past smokers with non-O blood type.

  14. Physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) for pulmonary application.

    PubMed

    Paranjpe, M; Finke, J H; Richter, C; Gothsch, T; Kwade, A; Büttgenbach, S; Müller-Goymann, C C

    2014-12-10

    For the development of any colloidal system, thorough characterization is extremely essential. This article discusses the physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) including stability analysis over 6 months time period for possible pulmonary administration for the treatment of pulmonary arterial hypertension (PAH). SLN consisting of phospholipid and triglycerides were manufactured using a novel microchannel homogenization method. These sildenafil-loaded SLN were then subjected to physicochemical characterization namely, particle size and distribution over shelf life, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and analysis of nebulization performance of these SLN by the means of next generation impactor (NGI). Additionally, the morphology of nebulized particles was assessed by transmission electron microscopy using negative staining technique. The solubility of sildenafil citrate and base in the lipid matrix was determined and was 0.1% w/w and 1% w/w, respectively. From the particle size measurements, it was observed that SLN without sildenafil demonstrated consistent particle sizes over 6 months. For the sildenafil-loaded SLN, increased particle sizes were found after manufacturing and further increased within weeks. From WAXD studies, after 6 months high intensity reflections corresponding to the stable β modification were observed. From DSC results, the peak minimum temperatures increased upon storage, hinting at a transformation to the stable β modification of triglycerides in the case of sildenafil-loaded SLN. Hence, it can be concluded that even small drug concentration influences particle size and stability.

  15. [Quantitative CT perfusion measurements in characterization of solitary pulmonary nodules: new insights and limitations].

    PubMed

    Mazzei, Maria Antonietta; Cioffi Squitieri, Nevada; Guerrini, Susanna; Di Crescenzo, Vincenzo; Rossi, Michele; Fonio, Paolo; Mazzei, Francesco Giuseppe; Volterrani, Luca

    2013-01-01

    Although computed tomography (CT) scans remain the basis of morphologic evaluation in the characterization of solitary pulmonary nodules (SPNs), perfusion CT can represent an additional feasible technique offering reproducible measurements, at least in SPNs with a diameter >10 mm. In particular, CT perfusion could reduce the number of SPNs, diagnosed as undetermined at morphologic CT, avoiding long term follow-up CT, FDG-PET studies, biopsy or unnecessary surgery with a significant reduction in healthcare costs. In order to reduce the radiation dose, an optimization of the CT perfusion protocol could be obtained using axial mode acquisition, using shorter acquisition time and adaptative statistical iterative reconstruction algorithm.

  16. Functional characterization of T cell populations in a mouse model of chronic obstructive pulmonary disease

    PubMed Central

    Eppert, Bryan L.; Wortham, Brian W.; Flury, Jennifer L.; Borchers, Michael T.

    2012-01-01

    Cigarette smoke (CS) exposure is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic peribronchial, perivascular and alveolar inflammation. The inflammatory cells consist primarily of macrophage, neutrophils and lymphocytes. Although myeloid cells are well studied, the role of lymphocyte populations in pathogenesis of COPD remains unclear. Using a mouse model of CS-induced emphysema our laboratory has previously demonstrated that CS exposure causes changes in the T cell receptor repertoire suggestive of an antigen specific response and triggers a pathogenic T cell response sufficient to cause alveolar destruction and inflammation. We extend these findings to demonstrate that T cells from CS-exposed mice of Balb/cJ or C57B6 strain are sufficient to transfer pulmonary pathology to CS-naïve, immunosufficient mice. CS exposure causes a proinflammatory phenotype among pulmonary T cells consistent with from COPD patients. We provide evidence that donor T cells from CS-exposed mice depend on antigen recognition to transfer alveolar destruction using MHC class I deficient recipient mice. Neither CD4+ nor CD8+ T cells from donor mice exposed to CS are alone sufficient to cause inflammation or pathology in recipient mice. We found no evidence of impaired suppression of T cell proliferation among regulatory T cells from CS-exposed mice. These results suggest that CS exposure initiates an antigen specific response that leads to pulmonary destruction and inflammation that involves both CD8+ and CD4+ T cells. These results are direct evidence for an autoimmune response initiated by CS exposure. PMID:23264660

  17. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model

    PubMed Central

    Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P.; Leopold, Jane A.; Hajjar, Roger J.

    2014-01-01

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca2+-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  18. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    PubMed

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-08-11

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells express hemoglobin α to control nitric oxide diffusion, but the role of this system in the pulmonary circulation has not been evaluated. We hypothesize that up-regulation of hemoglobin α in pulmonary endothelial cells contributes to nitric oxide depletion and pulmonary vascular dysfunction in pulmonary hypertension. Co-cultures of human pulmonary microvascular endothelial cells and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced pulmonary hypertension were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of hemoglobin α in pulmonary endothelium from humans and mice with pulmonary hypertension compared to controls. In addition, we show up-regulation of hemoglobin α in human pulmonary endothelial cells co-cultured with pulmonary artery smooth muscle cells in hypoxia. We treated pulmonary endothelial cells with a hemoglobin α mimetic peptide that disrupts the association of hemoglobin α with endothelial nitric oxide synthase, and found that cells treated with the peptide exhibited increased nitric oxide signaling compared to a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the hemoglobin α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial hemoglobin α functions as an endogenous scavenger of nitric oxide in the pulmonary endothelium. Targeting this pathway may offer a novel therapeutic target to increase endogenous levels of nitric oxide in pulmonary hypertension.

  19. Increase in blood viscosity in the sprinting horse: can it account for the high pulmonary arterial pressure?

    PubMed

    Fedde, M R; Erickson, H H

    1998-07-01

    Blood was taken from 49 Thoroughbred horses before and after racing at the track to determine if frusemide modified the apparent viscosity of the blood and to determine the effects of changes in shear rate and packed cell volume (PCV), associated with strenuous exercise, on apparent and relative viscosities. Small increases in apparent viscosity of the blood (at a specified PCV and shear rate) occurred in horses given frusemide compared to those receiving no frusemide; however, no differences were seen in relative viscosity. Although 2 groups of horses, those receiving frusemide before racing and those not receiving this drug were studied, the results suggest no influence of frusemide on any red blood cell variable that might modify apparent blood viscosity. Apparent viscosity of the blood was slightly (but significantly) higher after racing than before racing at any given PCV and shear rate, but relative viscosity was lower in the post race than in the prerace blood sample. The most important contributing factor to the increase in apparent viscosity in blood during racing is the increase in PCV, because the blood becomes nearly shear rate independent at shear rates likely to exist in the cardiovascular system during exercise. With an increase in PCV from 40 to 65% at shear rates above 225/s, apparent viscosity approximately doubled. However, this increase alone cannot account for the elevated pulmonary vascular pressure in the running horse, and additional factors, especially those causing the high left atrial pressure, must be considered. The cause of the elevated pressure may be multifactorial in nature.

  20. CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus erythematosus patients.

    PubMed

    Odler, B; Bikov, A; Streizig, J; Balogh, C; Kiss, E; Vincze, K; Barta, I; Horváth, I; Müller, V

    2017-05-01

    Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLEpulm, than in patients without pulmonary manifestations. CCL21 correlated negatively with DLCO ( r = -0.73; p < 0.01) and KLCO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DLCO/KLCO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

  1. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension.

    PubMed

    Doran, A K; Ivy, D D; Barst, R J; Hill, N; Murali, S; Benza, R L

    2008-07-01

    Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life. Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin). Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care of the central venous catheter. Patients are routinely counseled and advised regarding the risks of CR-BSIs and catheter care before central line insertion. Central line infections as well as bacteremia are well documented risks of chronic intravenous therapy and may significantly contribute to morbidity and mortality. Recent reports have suggested a possible increase in CR-BSI; therefore, the Scientific Leadership Council of the Pulmonary Hypertension Association decided to provide guidelines for good clinical practice regarding catheter care. Although data exits regarding patients with central venous catheters and the risk of blood stream infections in patients with cancer or other disorders, there is little data regarding the special needs of patients with pulmonary arterial hypertension requiring central venous access. These guidelines are extrapolated from the diverse body of literature regarding central venous catheter care.

  2. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  3. Pulmonary Embolism

    MedlinePlus

    ... is a sudden blockage in a lung artery. The cause is usually a blood clot in the leg called a deep vein thrombosis that breaks loose and travels through the bloodstream to the lung. Pulmonary embolism is a ...

  4. Pulmonary atresia

    MedlinePlus

    ... blood flow from the right ventricle (right side pumping chamber) to the lungs. In pulmonary atresia, a ... Reconstructing the heart as a single ventricle (1 pumping chamber instead of 2) Heart transplant Outlook (Prognosis) ...

  5. Counter-clockwise vortical blood flow in the main pulmonary artery in a patient with patent ductus arteriosus with pulmonary arterial hypertension: a cardiac magnetic resonance imaging case report.

    PubMed

    Reiter, Gert; Reiter, Ursula; Kovacs, Gabor; Adelsmayr, Gabriel; Greiser, Andreas; Stalder, Aurelien F; Olschewski, Horst; Fuchsjäger, Michael

    2016-08-08

    In patients with pulmonary hypertension (PH), duration of vortical blood flow along the main pulmonary artery enables estimation of the mean pulmonary arterial pressure (mPAP) non-invasively. It remains to date not known, if this method is applicable in patients with pulmonary arterial hypertension (PAH) and abnormal aortic-to-pulmonary shunting. The present case analyzes the effect of a patent ductus arteriosus (PDA) on pulmonary artery flow patterns in PAH (mPAP from right heart catheterization, 75 mmHg). PH-associated vortical blood flow, which is typically observed rotating in a clockwise direction when viewed in right ventricular outflow tract orientation, was found nested in PDA left-to-right shunting. Even though rotating counter-clockwise, duration of vortical flow translated into correct non-invasive mPAP estimate. This case indicates that PH-associated vortex rotation is not restricted to clockwise direction, and that vortex-based estimation of elevated mPAP might also be feasible in patients with PAH and PDA.

  6. Preparation and Characterization of Magnetic Nano-in-Microparticles for Pulmonary Delivery.

    PubMed

    McBride, Amber A; Price, Dominique N; Muttil, Pavan

    2017-01-01

    The purpose of this chapter is to detail the formulation and characterization of a magnetically-targeted drug delivery vehicle, termed nano-in-microparticles (NIMs), for pulmonary drug delivery. Currently, chemotherapeutics and antibiotics are delivered systemically and result in whole body side-effects. NIMs are formulated with superparamagnetic iron oxide nanoparticles, termed SPIONs, making these particles targetable to specific lung regions using a strong external magnet. Additionally, these particles can be formulated to contain any drug or therapeutic agent, such that a therapeutic dose can be delivered to a specific tissue location using the SPIONs-magnet interaction. Finally, these particles are in the appropriate size range for pulmonary delivery, making NIMs therapeutics feasibly inhalable.To generate these particles a solution containing lactose, SPIONs, and a microsphere dye (used as a drug surrogate) is spray-dried using a laboratory-scale spray dryer. The resulting dry powder microparticles (NIMs) can be characterized for their size and morphological properties by various techniques that are presented in this chapter.The utility of NIMs as a magnetic field-dependent targeting delivery platform in an in vivo mouse model has been demonstrated, and a protocol detailing the intratracheal delivery of NIMs dry powder is included as a separate chapter in this book.

  7. Bosentan Pharmacokinetics in Pediatric Patients with Pulmonary Arterial Hypertension: Comparison of Dried Blood Spot and Plasma Analysis.

    PubMed

    Géhin, Martine; Sidharta, Patricia N; Dingemanse, Jasper

    2016-01-01

    FUTURE-3, a phase III pediatric pharmacokinetic (PK) trial conducted to compare 2 bosentan dosing regimens in 64 patients with pulmonary arterial hypertension, offered the opportunity to compare dried blood spot (DBS)-derived data to plasma data. Bosentan PK parameters obtained with both methods were compared by the geometric mean ratio (GMR; DBS/plasma) and its 90% CI after correction for the blood-to-plasma partition ratio (0.6). Bosentan GMRs were 1.10 (1.03, 1.16) and 1.12 (1.04, 1.20) for AUCτ and Cmax, respectively. Bosentan concentrations measured by DBS were therefore good estimations of bosentan plasma concentrations. DBS can be considered a valid alternative to bosentan assessed in plasma. © 2016 S. Karger AG, Basel.

  8. Arterial blood gases, pulmonary function and pathology in rats exposed to 0. 75 or 1. 0 ppM ozone

    SciTech Connect

    Pepelko, W.E.; Mattox, J.K.; Yang, Y.Y.

    1980-06-01

    Arterial blood gases, residual lung volume (RV), deflation pressure volume (PV) curves, pulmonary pathology and body weight changes were studied in rats exposed up to 14 days to either 0.75 or 1.0 ppM ozone. Arterial PO2 and body weights decreased progressively with length of exposure while PaCO2 and RV increased. The slope of the PV curve decreased in all groups exposed to ozone. Pathological changes in the lung increased in severity with concentration and length of exposure. The present findings have shown that arterial blood gas measurements represent a sensitive index of altered lung function in rats, a species very sensitive to ozone exposure.

  9. Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

    PubMed Central

    Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

  10. A Modified Verhoeff-Van Gieson Elastin Histochemical Stain to Enable Pulmonary Arterial Hypertension Model Characterization

    PubMed Central

    Percival, K.R.; Radi, Z.A.

    2016-01-01

    Optimal histochemical staining is critical to ensure excellent quality stained sections to enable light microscopic and histomorphometric image analysis. Verhoeff-van Gieson is the most widely used histochemical stain for the visualization of vascular elastic fibers. However, it is notoriously difficult to differentiate fine elastic fibers of small vasculature to enable histomorphometric image analysis, especially in organs such as the lung. A tissue fixation procedure of 10% neutral buffered formalin with subsequent fixation in 70% ethanol further compounds the problem of small vessel staining and identification. Therefore, a modified Verhoeff’s elastin stain was developed as a reliable method to optimally highlight the internal and external elastic laminae of small arteries (50-100 µm external diameter) and intra-acinar vessels (10-50 µm external diameter) in 3 µm thick lung tissue sections from models of pulmonary arterial hypertension. This modified Verhoeff’s elastin stain demonstrated well-defined staining of fine elastic fibers of pulmonary blood vessels enabling subsequent histomorphometric image analysis of vessel wall thickness in small arteries and intra-acinar vessels. In conclusion, modification of the standard Verhoeff-van Gieson histochemical stain is needed to visualize small caliber vessels’ elastic fibers especially in tissues fixed in 10% neutral buffered formalin followed by additional fixation in 70% ethanol. PMID:26972717

  11. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    PubMed Central

    2012-01-01

    Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8

  12. The evaluation of pulmonary function and blood gas analysis in patients submitted to laparoscopic versus open nephrectomy

    PubMed Central

    Koc, Ayfer; Inan, Gozde; Bozkirli, Fusun; Coskun, Demet; Tunc, Lutfi

    2015-01-01

    ABSTRACT Background: The aim of this study was to assess the early postoperative pulmonary function and arterial blood gases in patients who have undergone open versus laparoscopic nephrectomy. Materials and Methods: Forty patients were randomly assigned to undergo laparoscopic (LN, n=20) or open nephrectomy (ON, n=20). Pulmonary function tests including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory volume at 25% (FEF25), forced expiratory volume at 50% (FEF50), forced expiratory volume at 25% to 75% (FEF25–75), forced expiratory volume in 1 second (FIV1) and peak expiratory flow (PEF) were performed one day before the operation and on the postoperative day 1. The arterial blood gas analysis (pH, pCO2, pO2, SaO2) was made at breathing room preoperatively, in the recovery phase and on postoperative day 1. Results: All spirometric variables decreased after both open and laparoscopic nephrectomy on postoperative day 1. FEV1, FVC, FEF25 and FEF25–75 values decreased on postoperative day 1 (39.7%, 37.4%, 27.7%, 51.8% respectively) in the open surgery group and they were significantly lower in laparoscopic group (29.9%, 32.5%, 23.2%, 44.5% respectively). There were no significant differences in FEF50, PEF and FIV1 between the groups. The SaO2 and pO2 values also decreased in both groups. During early recovery, pH decreased while pCO2 increased significantly but they returned to preoperative values on postoperative day 1 in both groups. Conclusion: Laparoscopic nephrectomy is better than open nephrectomy considering pulmonary functions. PMID:26742981

  13. The evaluation of pulmonary function and blood gas analysis in patients submitted to laparoscopic versus open nephrectomy.

    PubMed

    Koc, Ayfer; Inan, Gozde; Bozkirli, Fusun; Coskun, Demet; Tunc, Lutfi

    2015-01-01

    The aim of this study was to assess the early postoperative pulmonary function and arterial blood gases in patients who have undergone open versus laparoscopic nephrectomy. Forty patients were randomly assigned to undergo laparoscopic (LN, n=20) or open nephrectomy (ON, n=20). Pulmonary function tests including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory volume at 25% (FEF25), forced expiratory volume at 50% (FEF50), forced expiratory volume at 25% to 75% (FEF25-75), forced expiratory volume in 1 second (FIV1) and peak expiratory flow (PEF) were performed one day before the operation and on the postoperative day 1. The arterial blood gas analysis (pH, pCO2, pO2, SaO2) was made at breathing room preoperatively, in the recovery phase and on postoperative day 1. All spirometric variables decreased after both open and laparoscopic nephrectomy on postoperative day 1. FEV1, FVC, FEF25 and FEF25-75 values decreased on postoperative day 1 (39.7%, 37.4%, 27.7%, 51.8% respectively) in the open surgery group and they were significantly lower in laparoscopic group (29.9%, 32.5%, 23.2%, 44.5% respectively). There were no significant differences in FEF50, PEF and FIV1 between the groups. The SaO2 and pO2 values also decreased in both groups. During early recovery, pH decreased while pCO2 increased significantly but they returned to preoperative values on postoperative day 1 in both groups. Laparoscopic nephrectomy is better than open nephrectomy considering pulmonary functions.

  14. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

    PubMed

    Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

    2017-05-01

    Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.

  15. IBN NAFIS – A FORGOTTEN GENIUS IN THE DISCOVERY OF PULMONARY BLOOD CIRCULATION

    PubMed Central

    Akmal, M; Zulkifle, M; Ansari, AH

    2010-01-01

    Scientific theories take centuries to come into existence and they keep on evolving. Uncountable intellectual minds work on these theories; some fail to do anything about it; some add a little after tremendous efforts, and some people give remarkable and unforgettable contribution. As far as credit is concerned, the person who is able to prove the theory by his facts and who clears the maximum doubts by his observations, experimentations, facts and reasoning, gets the credit for that theory, and this should be done with honesty. The theory of pulmonary circulation took more than 2000 years to come into existence as we know it today. With the passage of time different people were given credit. Some say that it was given to Galen; some say it was Michael Servetus; others say that Realdus Columbus was the real discoverer; some gave the credit to Ibn Nafis, and finally people gave the credit to William Harvey. But after the rediscovery of Ibn Nafis’ manuscript no.62243 titled Sharah al Tashreeh al Qanoon, or “Commentary on the anatomy of Canon of Avicenna” in 1924 AD in Europe, it became clear that Ibn Nafis had described the pulmonary circulation almost 300 years before Harvey, and the historians like Aldo Mieli, Max Mayrhoff, Edward Coppola etc. clearly state that Ibn Nafis is the real discoverer of the pulmonary circulation and that he should be given the credit for the discovery of the pulmonary circulation. PMID:21042463

  16. More accurate quantification of pulmonary blood flow by magnetic resonance imaging than by lung perfusion scintigraphy in patients with fontan circulation.

    PubMed

    Fratz, Sohrab; Hess, John; Schwaiger, Markus; Martinoff, Stefan; Stern, Heiko C

    2002-09-17

    Quantitative evaluation of pulmonary perfusion using lung perfusion scintigraphy in patients with atriopulmonary anastomosis (APA) or total cavopulmonary connection (TCPC) or partial cavopulmonary connection (PCPC) is difficult because of preferential draining of the venae cavae to one lung. Scintigraphy is the gold standard. Phase-velocity MRI (PV-MRI) is a new technique for determining pulmonary perfusion. The aim of this study was therefore to determine whether PV-MRI is more accurate than scintigraphy for quantitative evaluation of pulmonary perfusion ratios in patients with APA, TCPC, or PCPC. We studied 15 patients with APA, TCPC, or PCPC (16+/-7 years old, 4 female). Twelve patients (15+/-8 years old, 3 female) with a single pulmonary blood source supplied by a subpulmonary ventricle, ensuring complete mixing of the radioactive tracer before entering the pulmonary circulation, served as controls. Pulmonary scintigraphy and PV-MRI were performed in all patients. Bland-Altman analysis showed a clinically unacceptable difference of 7.1% right pulmonary blood flow (27.2% upper and -13.0% lower limit of agreement) between the two methods in the study group. The two methods agreed excellently in the control group (difference, 1.6%; 4.0% upper and -7.2% lower limit of agreement), showing that the bad agreement in the study group was caused by the problems encountered using pulmonary scintigraphy in patients with APA, TCPC, or PCPC. Because of preferential caval flow into either lung, PV-MRI is more accurate for evaluating pulmonary perfusion ratios than lung perfusion scintigraphy in patients with Fontan-like circulation.

  17. Short-term effects of air pollution: a panel study of blood markers in patients with chronic pulmonary disease

    PubMed Central

    Hildebrandt, Katharina; Rückerl, Regina; Koenig, Wolfgang; Schneider, Alexandra; Pitz, Mike; Heinrich, Joachim; Marder, Victor; Frampton, Mark; Oberdörster, Günter; Wichmann, H Erich; Peters, Annette

    2009-01-01

    Background Growing evidence indicates that ambient air pollution is associated with exacerbation of chronic diseases like chronic pulmonary disease. A prospective panel study was conducted to investigate short-term changes of blood markers of inflammation and coagulation in response to daily changes in air pollution in Erfurt, Germany. 12 clinical visits were scheduled and blood parameters were measured in 38 male patients with chronic pulmonary disease during winter 2001/2002. Additive mixed models with random patient intercept were applied, adjusting for trend, weekday, and meteorological parameters. Hourly data on ultrafine particles (UFP, 0.01-0.1 μm), accumulation mode particles (ACP, 0.1-1.0 μm), PM10 (particulate matter <10 μm in diameter), elemental (EC) and organic carbon (OC), gaseous pollutants (nitrogen monoxide [NO], nitrogen dioxide [NO2], carbon monoxide [CO], and sulphur dioxide [SO2]) were collected at a central monitoring site and meteorological data were received from an official network. For each person and visit the individual 24-hour average of pollutants immediately preceding the blood withdrawal (lag 0) up to day 5 (lag1-4) and 5-day running means were calculated. Results Increased levels of fibrinogen were observed for an increase in one interquartile range of UFP, PM10, EC, OC, CO, and NO revealing the strongest effect for lag 3. E-selectin increased in association with ACP and PM10 with a delay of one day. The ACP effect was also seen with the 5-day-mean. The pattern found for D-dimer was inconsistent. Prothrombin fragment 1+2 decreased with lag 4 consistently for all particulate pollutants. Von Willebrand factor antigen (vWF) showed a consistent decrease in association with almost all air pollutants with all lags except for lag 0. No associations were found for C-reactive protein, soluble intercellular adhesion molecule 1, serum amyloid A and factor VII. Conclusion These results suggest that elevated concentrations of air pollution

  18. Characterization of 5-HT receptors on human pulmonary artery and vein: functional and binding studies

    PubMed Central

    Cortijo, Julio; Martí-Cabrera, Miguel; Bernabeu, Eva; Domènech, Teresa; Bou, Josep; Fernández, Andrés G; Beleta, Jorge; Palacios, José M; Morcillo, Esteban J

    1997-01-01

    presumably not involved in the contractile response to these agonists.Binding studies using selective radioligands for different 5-HT receptors could not detect the presence of 5-HT1A receptor binding in human pulmonary blood vessels whereas the 5-HT1B/1D radioligand [3H]-5-CT significantly labelled a population of specific binding sites in both vessel types. The presence of 5-HT2A receptors could also be inferred from the level of binding of [3H]-ketanserin to membranes obtained from human pulmonary vessels, although significance could not be reached for arteries. 5-HT4 specific receptor binding was scarce in veins and absent in the case of arteries.These findings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT1B/1D and 5-HT2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies. PMID:9421295

  19. Characterization of 5-HT receptors on human pulmonary artery and vein: functional and binding studies.

    PubMed

    Cortijo, J; Martí-Cabrera, M; Bernabeu, E; Domènech, T; Bou, J; Fernández, A G; Beleta, J; Palacios, J M; Morcillo, E J

    1997-12-01

    indicating that 5-HT1A, 5-HT3 and 5-HT4 receptors are presumably not involved in the contractile response to these agonists. 5. Binding studies using selective radioligands for different 5-HT receptors could not detect the presence of 5-HT1A receptor binding in human pulmonary blood vessels whereas the 5-HT(1B/1D) radioligand [3H]-5CT significantly labelled a population of specific binding sites in both vessel types. The presence of 5-HT2A receptors could also be inferred from the level of binding of [3H]-ketanserin to membranes obtained from human pulmonary vessels, although significance could not be reached for arteries. 5-HT4 specific receptor binding was scarce in veins and absent in the case of arteries. 6. These findings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT(1B/1D) and 5-HT2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies.

  20. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

    PubMed Central

    Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

    2004-01-01

    Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975. PMID:15175167

  1. Characterization of amphotericin B aerosols for inhalation treatment of pulmonary aspergillosis.

    PubMed

    Roth, C; Gebhart, J; Just-Nübling, G; von Eisenhart-Rothe, B; Beinhauer-Reeb, I

    1996-01-01

    In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or organ transplantation. For prophylaxis against Aspergillus infections, amphotericin B may be a useful drug when inhaled as aerosol. In this study, the aerosolization of amphotericin B was investigated using eight different medical nebulizers under various operating conditions and with different amphotericin B concentrations in the solution. The output of each nebulizer was characterized by the mass flow of spray (drug) leaving the mouthpiece and by the size distribution of the droplets. An effective prevention of pulmonary aspergillosis via amphotericin B inhalation requires a high pulmonary deposition of the drug within an acceptable time of administration associated with a low deposition in the oropharyngeal region. To evaluate the dosages of drug delivered by various types of nebulizers to different regions of the respiratory tract, a semi-empirical deposition model was applied which is based on experimental aerosol deposition data from over 20 normal adults. The main results of the study are: Solutions with amphotericin B concentrations up to 10 mg/ml can be converted into sprays by means of medical nebulizers without any problems. For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the production of the aerosol. To optimize amphotericin B treatment of the lungs via inhalation, sprays with mass flows above 100 mg/min and with mass median aerodynamic diameters (MMAD) below 3 microns should be slowly inhaled by the subject. Applying these criteria to the nebulizers investigated, three out of eight devices have proved suitable for amphotericin B treatment via inhalation.

  2. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

    PubMed

    Ourique, Aline Ferreira; Chaves, Paula Dos Santos; Souto, Gabriele Dadalt; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2014-12-18

    Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

  3. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

    PubMed

    Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

    2004-06-01

    Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975.

  4. Changes in systemic and pulmonary blood flow distribution in normal adult volunteers in response to posture and exercise: a phase contrast magnetic resonance imaging study.

    PubMed

    Wong, Derek T H; Lee, Kyong-Jin; Yoo, Shi-Joon; Tomlinson, George; Grosse-Wortmann, Lars

    2014-03-01

    Hemodynamics are usually evaluated in the supine position at rest. This is only a snapshot of an individual's daily activities. This study describes circulatory adaptation, as assessed by magnetic resonance imaging, to changes in position and exercise. Phase contrast magnetic resonance imaging of blood flow within systemic and pulmonary arteries and veins was performed in 24 healthy volunteers at rest in the prone and supine position and with bicycle exercise in the supine position. No change was seen in systemic blood flow when moving from prone to supine. Exercise resulted in an increased percentage of cardiac output towards the lower body. Changes in position resulted in a redistribution of blood flow within the left lung--supine positioning resulted in decreased blood flow to the left lower pulmonary vein. With exercise, both the right and left lower lobes received increased blood flow, while the upper lobes received less.

  5. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  6. Tracking pulmonary gas exchange by breathing control during exercise: role of muscle blood flow

    PubMed Central

    Haouzi, Philippe

    2014-01-01

    Populations of group III and IV muscle afferent fibres located in the adventitia of the small vessels appear to respond to the level of venular distension and to recruitment of the vascular bed within the skeletal muscles. The CNS could thus be informed on the level of muscle hyperaemia when the metabolic rate varies. As a result, the magnitude and kinetics of the change in peripheral gas exchange – which translates into pulmonary gas exchange – can be sensed. We present the view that the respiratory control system uses these sources of information of vascular origin, among the numerous inputs produced by exercise, as a marker of the metabolic strain imposed on the circulatory and the ventilatory systems, resulting in an apparent matching between pulmonary gas exchange and alveolar ventilation. PMID:23981720

  7. Characterizing blood cells by biophysical measurements in flow.

    PubMed

    Groner, W; Tycko, D

    1980-01-01

    One effect of automation in the hematology laboratory has been to introduce new characterizations of blood cells. Resistive pulse sensing (Coulter) and light scatter measurements in flow provide rapid and reproducible cell counts. They also provide information about red cell size, shape, and deformability. Thus, they have provided new characterization of these cells in terms of their biophysical properties. Leukocytes have been classified by optical scatter and absorption measurements in flow after being stained cytochemically. This provides rapid and precise WBC differential counts. However, here again, additional information about relative cell-enzyme content or activity is also accessible to provide a new characterization of the leukocytes. The ultimate range of utility of this expanding technology in the automated hematology laboratory of the future will, of course, depend upon establishing relations between the biophysical parameters and the functions of the cells. This, in turn, must depend upon the use of the technology by researchers and clinicians in studying cell function and the aberrations of these functions which define disease.

  8. A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

    PubMed Central

    SOTIRIOU, GEORGIOS A.; DIAZ, EDGAR; LONG, MARK S.; GODLESKI, JOHN; BRAIN, JOSEPH; PRATSINIS, SOTIRIS E.; DEMOKRITOU, PHILIP

    2013-01-01

    A novel method is presented which is suitable for assessing in-vivo the link between the physico-chemical properties of engineered nanomaterials (ENMs) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in-vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects. PMID:21809902

  9. Pulmonary Vasculitis

    PubMed Central

    Brown, Kevin K.

    2006-01-01

    Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody–associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex–mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody–associated disorder, vasculitides. PMID:16493151

  10. Aerobic exercise-related attenuation of arterial pulmonary hypertension: A right arrow targets the disease?

    PubMed

    Madonna, Rosalinda; De Caterina, Raffaele; Geng, Yong-Jian

    2016-12-01

    Characterized by progressive elevation of mean pulmonary artery pressure and pulmonary vascular resistance, pulmonary arterial hypertension (PAH) is an important health problem that contributes to right heart failure. Pulmonary arterial remodeling and constriction are two prominent features of PAH. It is a traditional view that increasing pulmonary blood flow and pressure, aerobic exercise does more harm than good to the pulmonary vasculature in PAH. However, recent studies have documented a potential benefit of low-intensity aerobic exercise for PAH patients. Here the current mini-review outlines the evidence and challenges for this additional tool in our armamentarium to combat this ominous disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Blood gases and pulmonary blood flow during resuscitation of very preterm lambs treated with antenatal betamethasone and/or Curosurf: effect of positive end-expiratory pressure.

    PubMed

    Crossley, Kelly J; Morley, Colin J; Allison, Beth J; Polglase, Graeme R; Dargaville, Peter A; Harding, Richard; Hooper, Stuart B

    2007-07-01

    Resuscitation of very premature lambs with positive end-expiratory pressure (PEEP) improves oxygenation and reduces pulmonary blood flow (PBF). However, the effects of PEEP on blood gases and PBF have not been studied in preterm lambs receiving antenatal corticosteroids or postnatal surfactant. Lambs were delivered at 125 d of gestation (term 147 d) and ventilated with a tidal volume (VT) of 5 mL/kg using different levels of PEEP. Four treatment groups were studied: (1) antenatal betamethasone 24 and 36 h before delivery; (2) postnatal Curosurf; (3) antenatal betamethasone and postnatal Curosurf; (4) untreated controls. Blood gases, PBF, and ventilator parameters were recorded during the first 2 h. Increasing PEEP improved oxygenation even after antenatal betamethasone and postnatal Curosurf, without adverse effects on arterial PCO2. Increasing PEEP reduced PBF; this effect was not altered by betamethasone and/or Curosurf. In very preterm lambs ventilated with fixed VT, increasing levels of PEEP improved oxygenation after antenatal glucocorticoids and/or postnatal surfactant. These treatments do not alter the deleterious effects of high levels of PEEP on PBF.

  12. Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent: preliminary results in a rabbit model.

    PubMed

    Burke, Stephen J; Annapragada, Ananth; Hoffman, Eric A; Chen, Emmanuel; Ghaghada, Ketan B; Sieren, Jered; van Beek, Edwin J R

    2007-03-01

    Polyethylene glycol-coated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Also, visualization of the (real-time) therapeutic effects of tissue plasminogen activator (t-PA) on pulmonary embolism (PE) was attempted. Six rabbits (weight approximately 4 kg) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml; GE HealthCare, Princeton, NJ) at a dose of 1400 mg I per animal, and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mg I/animal). Subsequently, five animals were injected with 2 mg of t-PA and imaging continued for up to 4(1/2) hours. Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited nonuniform opacification and rapid clearance postinjection. Three of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10-57%, mean 42%). One animal showed no response to t-PA. Liposomal blood pool agents effectively identified acute PE without need for reinjection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections.

  13. Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent – preliminary results in a rabbit model

    PubMed Central

    Burke, Stephen J; Annapragada, Ananth; Hoffman, Eric A; Chen, Emmanuel; Ghaghada, Ketan B; Sieren, Jered; van Beek, Edwin JR

    2007-01-01

    Hypothesis and Objectives PEGylated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Secondly, visualization of the (real-time) therapeutic effects of tissue-Plasminogen Activator (t-PA) on pulmonary embolism (PE) was attempted. Materials and Methods Six rabbits (approximate 4 kg weight) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml, GE HealthCare, Princeton, NJ) at a dose of 1400 mgI per animal and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mgI/animal). Subsequently, five animals were injected with 2mg t-PA and imaging continued for up to 4 ½ hours. Results Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited non uniform opacification and rapid clearance post injection. Three out of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, Pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10–57%, mean 42%). One animal showed no response to t-PA. Conclusions Liposomal blood pool agents effectively identified acute PE without need for re-injection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections. PMID:17307669

  14. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    PubMed Central

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

  15. Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management.

    PubMed

    Ostrea, Enrique M; Villanueva-Uy, Esterlita T; Natarajan, Girija; Uy, Herbert G

    2006-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is characterized by severe hypoxemia shortly after birth, absence of cyanotic congenital heart disease, marked pulmonary hypertension, and vasoreactivity with extrapulmonary right-to-left shunting of blood across the ductus arteriosus and/or foramen ovale. In utero, a number of factors determine the normally high vascular resistance in the fetal pulmonary circulation, which results in a higher pulmonary compared with systemic vascular pressure. However, abnormal conditions may arise antenatally, during, or soon after birth resulting in the failure of the pulmonary vascular resistance to normally decrease as the circulation evolves from a fetal to a postnatal state. This results in cyanosis due to right-to-left shunting of blood across normally existing cardiovascular channels (foramen ovale or ductus arteriosus) secondary to high pulmonary versus systemic pressure. The diagnosis is made by characteristic lability in oxygenation of the infant, echocardiographic evidence of increased pulmonary pressure, with demonstrable shunts across the ductus arteriosus or foramen ovale, and the absence of cyanotic heart disease lesions. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilatation, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide has been one of the latest measures to successfully treat PPHN and significantly reduce the need for extracorporeal membrane oxygenation.

  16. Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles

    PubMed Central

    Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Berenstein, Laura Diaz; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

    2016-01-01

    Objective Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. Methods 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3–9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. Results A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=−0.67–−0.70 for all patients on room air, p<0.01 and R=−0.49–−0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. Conclusions There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. Trial Registration Number NCT02135081. PMID:26048877

  17. Nano-liposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary pharmacokinetics

    PubMed Central

    Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

    2007-01-01

    The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% ± 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 ± 0.8 μm, maximum fine particle fraction (FPF) of 71.1 ± 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 ± 0.1 μm, and geometric standard deviation (GSD) 1.7 ± 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi’s Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection. PMID:18203434

  18. Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease.

    PubMed Central

    Howes, T. Q.; Keilty, S. E.; Maskrey, V. L.; Deane, C. R.; Baudouin, S. V.; Moxham, J.

    1996-01-01

    BACKGROUND: L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the production of NO. This has been shown by local infusion in peripheral vascular beds but there are few studies of the effects during systemic infusion. Renal vasoconstriction is known to be important in the pathogenesis of cor pulmonale in patients with hypoxic chronic obstructive pulmonary disease (COPD). The effects of a systemic infusion of L-arginine on renal and aortic haemodynamics were therefore investigated in normal subjects and in patients with hypoxic COPD. METHODS: Ten normal volunteers were recruited from the research staff of King's College Hospital Six patients with COPD and hypoxia (arterial oxygen tension (PaO2) < 8.5 kPa) were recruited from the thoracic medicine outpatient clinic at King's College Hospital and five age and sex matched normal subjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volunteers for medical research. There was no history of renal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) of blood flow in intrarenal arteries were obtained using colour flow Doppler ultrasound. Using the same technique, Vmax was obtained from the abdominal aorta just distal to the xiphisternum before and after infusion of L-arginine via a large peripheral vein (20 g in 100 ml sterile water over 30 minutes). RESULTS: In normal subjects L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.22 m/s to 0.26 m/s, an increase of 19.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. L-arginine had no effect on intrarenal or aortic blood velocity in patients with hypoxic COPD. In age matched controls L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.20 m/s to 0

  19. Living with Pulmonary Embolism

    MedlinePlus

    ... on Twitter. Living With Pulmonary Embolism Pulmonary embolism (PE) usually is treated in a hospital. After leaving ... you're taking medicine. Medicines used to treat PE can thin your blood too much. This can ...

  20. What Causes Pulmonary Embolism?

    MedlinePlus

    ... this page from the NHLBI on Twitter. What Causes Pulmonary Embolism? Major Causes Pulmonary embolism (PE) usually begins as a blood ... from surgery or injured in other ways. Other Causes Rarely, an air bubble, part of a tumor, ...

  1. Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

    PubMed

    Aragon, Mario J; Topper, Lauren; Tyler, Christina R; Sanchez, Bethany; Zychowski, Katherine; Young, Tamara; Herbert, Guy; Hall, Pamela; Erdely, Aaron; Eye, Tracy; Bishop, Lindsey; Saunders, Samantha A; Muldoon, Pretal P; Ottens, Andrew K; Campen, Matthew J

    2017-03-07

    Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

  2. Effects of pentoxifylline on some peripheral blood parameters and haemostasis in acute pulmonary tissue injury after cyclophosphamide.

    PubMed

    Sulkowska, M; Musiatowicz, B; Sulkowski, S; Giedrojć, J; Sulik, M; Jakubowski, A; Terlikowski, S; Pasztaleniec, L; Baltaziak, M; Sobaniec-Lotowska, M

    1997-01-01

    Cyclophosphamide (CP) is one of the widely used cytostatic drugs, with a strong toxic influence on pulmonary tissue. Experimental works have shown that a single high dose of CP causes injury to all elements of the interalveolar septum, especially to the alveolar endothelial and epithelial cells. The aim of this work was to evaluate the influence of pentoxifylline (PTXF) (30 mg/kg b.w.) on the ultrastructure of lungs capillaries and blood cell count as well as plasma fibrinogen levels in Wistar rats after intraperitoneal injection of 150 mg/b.w. CP. We established that in the doses applied PTXF had no statistically significant influence on the number of leukocytes and erythrocytes determined in the left ventricular blood of rats receiving CP, while the number of white cells from animals given PTXF only was higher than in controls. There was a smaller decrease in the number of platelets (p < 0.05) and smaller reduction in fibrinogen level (p < 0.01) in the serum of PTXF-CP animals than in the CP group. The results obtained suggest a protective effect of PTXF on CP induced changes, which have been evidenced in some of the parameters examined. Ultrastructural examinations found the lungs to be the organ of extramedullary thrombocytopoiesis in CP-treated animals and revealed that platelet accumulation in the system of lung capillaries was a potential cause of the decrease observed in the number of blood platelets following CP administration.

  3. Right ventricular remodeling in pulmonary hypertension.

    PubMed

    Franco, Veronica

    2012-07-01

    The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

  4. The influence of sleeping position on functional residual capacity and effective pulmonary blood flow in healthy neonates.

    PubMed

    Aiton, N R; Fox, G F; Alexander, J; Ingram, D M; Milner, A D

    1996-12-01

    Variation in body position has been shown to affect respiratory function in adults and neonates with and without respiratory illness. At present it remains unclear why respiratory function should be affected by different body positions. We hypothesized that the effect of body weight on the relatively compliant chest wall of the newborn infant in the prone position would cause a reduction in functional residual capacity (FRC) and a compensatory improvement in ventilation/perfusion matching as measured by effective pulmonary blood flow. To evaluate this, a paired crossover study was performed on 12 normal newborn infants. The inert gas (argon) rebreathing method adapted for neonates was used to measure FRC. Simultaneously effective pulmonary blood flow (Qpeff) was determined using Freon 22 and a mass spectrometer with computerized analysis. The babies were studied in three different positions in random order: prone, supine and right lateral decubitus. The means (95% confidence intervals) of the three groups of FRC were 23.8 (19.2 to 28.4), 23.8 (20.2 to 27.5), and 24.3 (19.5 to 29.2) ml/kg, respectively (P = 0.59) and for Qpeff were 104 (91 to 116), 108 (95 to 122), 109 (97 to 122) ml/ kg-min, respectively (P = 0.11). Thus no significant differences were demonstrated. In nine of the babies, a repeat supine measurement was taken at the end of the study to assess repeatability of the method. In these nine babies alone the results were 22.7 (19.1 to 26.3) and 22.1 (18.6 to 25.6) ml/kg for FRC, and 102 (89 to 116) and 98 (90 to 107) ml/kg-min for Qpeff. The coefficients of repeatability were 4.7 ml/kg for FRC (21%) and 30 ml/kg-min for Qpeff (30%).

  5. PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

    2012-01-01

    Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

  6. Radionuclide-determined changes in pulmonary blood volume and thallium lung uptake in patients with coronary artery disease

    SciTech Connect

    Wilson, R.A.; Okada, R.D.; Boucher, C.A.; Strauss, H.W.; Pohost, G.M.

    1983-03-01

    Exercise-induced increases in radionuclide-determined pulmonary blood volume (PBV) and thallium lung uptake have been described in patients with coronary artery disease (CAD) and have been shown to correlate with transient exercise-induced left ventricular dysfunction. To compare these 2 techniques in the same patients, 74 patients (59 with and 15 without significant CAD) underwent supine bicycle exercise twice on the same day--first for thallium myocardial and lung imaging and then for technetium-99m gated blood pool imaging for the PBV ratio determination. Thallium activity of lung and myocardium was determined to calculate thallium lung/heart ratio. Relative changes in PBV from rest to exercise were expressed as a ratio of pulmonary counts (exercise/rest). Previously reported normal ranges for thallium lung/heart ratio and PBV ratio were used. The PBV ratio and thallium lung/heart ratio were abnormal in 71 and 36%, respectively, of patients with CAD (p less than 0.01). Both ratios were normal in all patients without CAD. Although the resting ejection fractions did not differ significantly in patients with normal versus those with abnormal PBV ratios or thallium lung/heart ratios, abnormal PBV ratios and thallium lung/heart ratios were associated with an exercise-induced decrease in ejection fraction. Propranolol use was significantly higher in patients with abnormal than in those with normal thallium lung/heart ratios (p less than 0.01). No significant difference in propranolol use was present in patients with abnormal or normal PBV ratios. In conclusion: (1) the prevalence of an abnormal thallium lung/heart ratio is less than that of the PBV ratio in patients with CAD; (2) both tests are normal in normal control subjects; (3) propranolol does not cause abnormal results in normal control subjects; however, propranolol may influence lung thallium uptake in patients with CAD; and (4) when both tests are abnormal, there is a high likelihood of multivessel disease.

  7. [Noninvasive determination of the ratio of pulmonary to systemic blood flow with two-dimensional Doppler echocardiography: efficacy and limitation].

    PubMed

    Okamoto, M; Miyatake, K; Kinoshita, N; Nakasone, I; Ohwa, M; Takao, S; Fusejima, K; Sakakibara, H; Nimura, Y

    1984-06-01

    Noninvasive determination of the ratio of the pulmonary to systemic blood flow (Qp/Qs) was attempted in 31 cases with intracardiac shunt using two-dimensional pulsed Doppler echocardiography. The Qp/Qs of these cases was ranged from 0.99 to 4.55 with an average of 2.63 by cardiac catheterization. Technical problems in the measurement were also studied. Seventeen cases with no shunt were served as controls. Systemic and pulmonary flow volumes, Qp and Qs (ml/min), were calculated by the following equation: Q (ml/min) = mean flow velocity (cm/sec) X cross sectional area of the semilunar valve ring (cm2) X 60 Here, the sample volume was set in the center of the valve ring at the phase when the flow velocity attained its peak in a pulse period. The mean velocity was obtained by dividing the integration of instantaneous mean frequency in the sample volume for a pulse period by RR interval. The ultrasonic incident angle was measured on the echocardiogram. The velocity profile at the valve ring was assumed to be a plane wave. The diameter (D) of the valve ring was measured on the echocardiograms of the long-axis view of the outflow tract. To make a correction referring to the value obtained by angiocardiography, 0.22 cm was added to the value obtained on the echocardiogram (D). The cross sectional area of the valve ring was calculated according to the following formula: Cross sectional area (cm2) = pi X [(D + 0.22/2)]2 The Qp/Qs ratio by the Doppler method in the cases with no intracardiac shunt was 1.11 (S.D. = 0.21) on an average and the Qp/Qs in the cases with an intracardiac shunt was well correlated with that by catheterization (r = 0.82). These results suggested the feasibility of the clinical application of the Doppler method for noninvasive determination of Qp/Qs. In 17 cases, pulmonary and systemic flow volumes measured by the direct Fick method were compared with those by the Doppler method, respectively. Considerable differences were observed between them. There

  8. [Expression of PAI-2 mRNA in peripheral blood leucocytes and regulation by sGC activator in pulmonary hypertension].

    PubMed

    Zou, L H; Zhang, S; Xu, X M; Xiao, F; Zhai, Z G

    2016-04-26

    To investigate the mRNA expression level of plasminogen activator inhibitor-2 (PAI-2) in peripheral blood leucocytes and regulation by soluble guanylate cyclase (sGC) activator in pulmonary hypertension. The human pulmonary arterial smooth muscle cells were treated with sGC activator Cinaciguat. The mRNA and protein expression levels of PAI-2 were detected with Real-time PCR and Western blot. The fresh blood samples of 8 patients with pulmonary arterial hypertension (PAH) (collected at the China-Japan Friendship Hospital from November 2014 to March 2015), 16 patients with chronic thromboembolic pulmonary hypertension (CTEPH) (collected at the China-Japan Friendship Hospital from November 2014 to March 2015), 24 age- and gender- matched healthy controls (collected at Beijing Hospital in March 2015) were treated with Cinaciguat for 8 hours. Then RNA of peripheral leukocytes was extracted and performed with reverse transcription and Real-time PCR to detect the mRNA level of PAI-2, which was compared between healthy controls and patients with pulmonary hypertension, before and after the treatment of Cinaciguat. At last, the correlation of PAI-2 mRNA level and the clinic severity of pulmonary hypertension were identified. The mRNA and protein expression levels of PAI-2 were promoted by Cinaciguat in human pulmonary arterial smooth muscle cells. The baseline mRNA level of PAI-2 in peripheral leukocytes was significantly lower in PAH patients compared to the healthy controls (0.201±0.152, 0.660±0.440, P=0.021). There was no significant difference in the mRNA expression level of PAI-2 between the CTEPH patients and controls (0.428±0.364, 0.769±0.682, P=0.152). After Cinaciguat treatment, the mRNA expression levels of PAI-2 were up-regulated in PAH patients and CTEPH patients (1.352±1.127, 1.203±1.008), there was no significant difference in the mRNA expression level of PAI-2 among the PAH patients, CTEPH patients and controls (P=0.130, P=0.534). The baseline m

  9. Pulmonary MRI at 3T: Non-enhanced pulmonary magnetic resonance Imaging Characterization Quotients for differentiation of infectious and malignant lesions.

    PubMed

    Nagel, Sebastian Niko; Kim, Damon; Penzkofer, Tobias; Steffen, Ingo G; Wyschkon, Sebastian; Hamm, Bernd; Schwartz, Stefan; Elgeti, Thomas

    2017-04-01

    To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions. Thirty-eight pulmonary lesions in 29 patients were evaluated. Seventeen patients were immunocompromised (11 infections and 6 lymphomas) and 12 served as controls (4 bacterial pneumonias, 8 solid tumors). Ten of the 15 infections were acute. Signal intensities (SI) were measured in the lesion, chest wall muscle, and subcutaneous fat. Scaled SIs as Non-enhanced Imaging Characterization Quotients ((SILesion-SIMuscle)/(SIFat-SIMuscle)*100) were calculated from the T2-weighted images using the mean SI (T2-NICQmean) or the 90th percentile of SI (T2-NICQ90th) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Qmean: SILesion/SIMuscle). Infectious pulmonary lesions showed a higher T2-NICQmean (40.1 [14.6-56.0] vs. 20.9 [2.4-30.1], p<0.05) and T2-NICQ90th (74.3 [43.8-91.6] vs. 38.5 [15.8-48.1], p<0.01) than malignant lesions. T1-Qmean was higher in malignant lesions (0.85 [0.68-0.94] vs. 0.93 [0.87-1.09], p<0.05). Considering infections only, T2-NICQ90th was lower when anti-infectious treatment was administered >24h prior to MRI (81.8 [71.8-97.6] vs. 41.4 [26.6-51.1], p<0.01). Using Youden's index (YI), the optimal cutoff to differentiate infectious from malignant lesions was 43.1 for T2-NICQmean (YI=0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ90th (YI=0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ90th and T1-Qmean increased diagnostic performance (YI=0.72, 0.77 sensitivity, 0.95 specificity). Considering each quotient alone, T2-NICQ90th showed the best diagnostic performance and could allow differentiation of acute infectious from malignant pulmonary lesions with high specificity. Combining T2-NICQ90th with T1-Qmean increased overall performance, especially regarding sensitivity

  10. Characterization of red blood cells (RBCs) using dual Brillouin/Raman micro-spectroscopy

    NASA Astrophysics Data System (ADS)

    Meng, Zhaokai; Bustamante-Lopez, Sandra C.; Yakovlev, Vladislav V.; Meissner, Kenith E.

    2016-04-01

    Erythrocytes, or red blood cells, transport oxygen to and carbon dioxide from the body's tissues and organs. Red blood cell mechanical properties are altered in a number of diseases such as sickle cell anaemia and malaria. Additionally, mechanically modified red blood cell ghosts are being considered as a long-term, biocompatible carrier for drug delivery and for blood analyte sensing. Brillouin spectroscopy enables viscoelastic characterization of samples at the microscale. In this report, Brillouin spectroscopy is applied to characterize the mechanical properties of red blood cells and red blood cell ghosts.

  11. Application of Gemstone Spectral Computed Tomography Imaging in the Characterization of Solitary Pulmonary Nodules: Preliminary Result.

    PubMed

    Lin, Ji-Zheng; Zhang, Liang; Zhang, Chuan-Yu; Yang, Lei; Lou, He-Nan; Wang, Ze-Guo

    .05). Dual-energy CT gemstone spectral imaging provides a novel method to better characterize pulmonary nodules in double-phase contrast-enhanced scanning.

  12. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands

    PubMed Central

    Ning, Fangkun; Wang, Chao; Berry, Karin Zemski; Kandasamy, Pitchaimani; Liu, Haolin; Murphy, Robert C.; Voelker, Dennis R.; Nho, Chu Won; Pan, Choel-Ho; Dai, Shaodong; Niu, Liwen; Chu, Hong-Wei; Zhang, Gongyi

    2014-01-01

    The short palate, lung and nasal epithelial clone 1 (SPLUNC1) protein is a member of the palate, lung, and nasal epithelium clone (PLUNC) family, also known as bactericidal/permeability-increasing (BPI) fold-containing protein, family A, member 1 (BPIFA1). SPLUNC1 is an abundant protein in human airways, but its function remains poorly understood. The lipid ligands of SPLUNC1 as well as other PLUNC family members are largely unknown, although some reports provide evidence that lipopolysaccharide (LPS) could be a lipid ligand. Unlike previous hypotheses, we found significant structural differences between SPLUNC1 and BPI. Recombinant SPLUNC1 produced in HEK 293 cells harbored several molecular species of sphingomyelin and phosphatidylcholine as its ligands. Significantly, in vitro lipid-binding studies failed to demonstrate interactions between SPLUNC1 and LPS, lipoteichoic acid, or polymyxin B. Instead, one of the major and most important pulmonary surfactant phospholipids, dipalmitoylphosphatidylcholine (DPPC), bound to SPLUNC1 with high affinity and specificity. We found that SPLUNC1 could be the first protein receptor for DPPC. These discoveries provide insight into the specific determinants governing the interaction between SPLUNC1 and lipids and also shed light on novel functions that SPLUNC1 and other PLUNC family members perform in host defense.—Ning, F., Wang, C., Berry, K. Z., Kandasamy, P., Liu, H., Murphy, R. C., Voelker, D. R., Nho, C. W., Pan, C.-H., Dai, S., Niu, L., Chu, H.-W., Zhang, G. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands. PMID:25223608

  13. Three-dimensional MR pulmonary perfusion imaging and angiography with an injection of a new blood pool contrast agent B-22956/1.

    PubMed

    Zheng, J; Carr, J; Harris, K; Saker, M B; Cavagna, F M; Maggioni, F; Laub, G; Li, D; Finn, J P

    2001-10-01

    Initial evaluation of a new blood pool agent, B-22956/1, for pulmonary imaging was performed in five domestic pigs with artificial embolism. Pre-embolism 3D pulmonary perfusion images were first acquired by injecting an extravascular agent, gadoteridol. The pulmonary arteries of the pigs were then occluded by the artificial emboli. Post-embolism perfusion scans were subsequently performed by injecting B-22956/1. Additional post-embolism high-spatial-resolution angiograms were also acquired. Parenchyma perfusion deficits were well depicted in the post-embolism perfusion maps. The post-embolism angiography clearly revealed the location and extent of the filling defects in the pulmonary vessels. Signal intensities of perfusion maps on the normal parenchyma were significantly improved (30%) by using B-22956/1, in comparison with perfusion images using gadoteridol (P < 0.01). Many pulmonary angiograms with approximately equal contrast could be obtained even at 22 minutes after the injection of B-22956/1. Our initial results indicate that blood pool agent B-22956/1 may provide opportunities for whole-lung-coverage perfusion mapping and additional high-resolution target angiograms after a single injection.

  14. Enhanced characterization of solid solitary pulmonary nodules with Bayesian analysis-based computer-aided diagnosis

    PubMed Central

    Perandini, Simone; Soardi, Gian Alberto; Motton, Massimiliano; Augelli, Raffaele; Dallaserra, Chiara; Puntel, Gino; Rossi, Arianna; Sala, Giuseppe; Signorini, Manuel; Spezia, Laura; Zamboni, Federico; Montemezzi, Stefania

    2016-01-01

    The aim of this study was to prospectively assess the accuracy gain of Bayesian analysis-based computer-aided diagnosis (CAD) vs human judgment alone in characterizing solitary pulmonary nodules (SPNs) at computed tomography (CT). The study included 100 randomly selected SPNs with a definitive diagnosis. Nodule features at first and follow-up CT scans as well as clinical data were evaluated individually on a 1 to 5 points risk chart by 7 radiologists, firstly blinded then aware of Bayesian Inference Malignancy Calculator (BIMC) model predictions. Raters’ predictions were evaluated by means of receiver operating characteristic (ROC) curve analysis and decision analysis. Overall ROC area under the curve was 0.758 before and 0.803 after the disclosure of CAD predictions (P = 0.003). A net gain in diagnostic accuracy was found in 6 out of 7 readers. Mean risk class of benign nodules dropped from 2.48 to 2.29, while mean risk class of malignancies rose from 3.66 to 3.92. Awareness of CAD predictions also determined a significant drop on mean indeterminate SPNs (15 vs 23.86 SPNs) and raised the mean number of correct and confident diagnoses (mean 39.57 vs 25.71 SPNs). This study provides evidence supporting the integration of the Bayesian analysis-based BIMC model in SPN characterization. PMID:27648166

  15. Organic cation transporters in the blood-air barrier: expression and implications for pulmonary drug delivery.

    PubMed

    Salomon, Johanna Jessica; Ehrhardt, Carsten

    2012-06-01

    Studies concerning the impact that hepatic, renal and intestinal transporters have on drug disposition have been frequently reported in the literature. Surprisingly, however, little is known regarding the distribution and function of drug-transporter proteins of the lung epithelium. Many drugs (delivered to the lung) have a net positive charge and, thus, are potential substrates of organic cation transporters; currently marketed compounds (e.g., bronchodilators), as well as novel drug candidates in development, are such substrates. It is the aim of this review to summarize the current state of organic cation-transporter expression analysis in the lung and in in vitro models of bronchial and alveolar barriers. Moreover, activity of selected transporters in lung epithelium in situ and in vitro will be highlighted, and their potential role in pulmonary drug disposition will be addressed. One example included here is the transporter-dependent absorption of beta2-agonists in respiratory epithelial cells.

  16. Relationship between changes in pulmonary V̇O₂ kinetics and autonomic regulation of blood flow.

    PubMed

    McNarry, M A; Kingsley, M I C; Lewis, M J

    2014-08-01

    Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.

  17. Imbalance between subsets of CD8+ peripheral blood T cells in patients with chronic obstructive pulmonary disease

    PubMed Central

    Zhang, Ming-Qiang; Liu, Hong-Ju; Xin, Jian-Bao; Zhang, Jian-Chu; Wu, Jiang-Hua; Meng, Zhao-Ji; Sun, Sheng-Wen

    2016-01-01

    Background. CD8+ T lymphocytes are known to play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, systematic analyses of CD8+ T cell (Cytotoxic T cells, Tc) subsets in COPD patients have yet to be well conducted. Methods. The whole Tc subsets, including Tc1/2/10/17, CD8+ regulatory T cells (Tregs) and CD8+α7+ T cells, were quantified by flow cytometry in peripheral blood from 24 stable COPD subjects (SCOPD), 14 patients during acute exacerbations (AECOPD), and 14 healthy nonsmokers (HN). Results. Acute exacerbations of COPD were accompanied by elevated levels of circulating CD8+ T cells. Tc1 cells were increased in both SCOPD and AECOPD patients, whereas the percentage of Tc2 cells was decreased in SCOPD patients but remained normal in AECOPD patients. Tc17 cells were increased only in AECOPD patients, and the percentage of Tc10 cells was reduced in both SCOPD and AECOPD patients. The imbalances of pro/anti-inflammatory Tc subsets observed in COPD may be caused by the lack of Tc10 cells and the impaired anti-inflammatory capacity of CD8+ Tregs. Conclusions. The imbalances between subsets of CD8+ peripheral blood T cells contribute to the immune response dysfunction in COPD pathogenesis. PMID:27547589

  18. Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels.

    PubMed

    Gao, Feng; Li, Ming; Ge, Xiaojun; Zheng, Xiangpeng; Ren, Qingguo; Chen, Yan; Lv, Fangzhen; Hua, Yanqing

    2013-12-01

    To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. Of 108 GGNs, 10 were benign, 24 preinvasive nodules and 74 adenocarcinomas that were pathologically proven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant.

  19. Oxidant-antioxidant balance in the blood of patients with chronic obstructive pulmonary disease after smoking cessation.

    PubMed

    Woźniak, Alina; Górecki, Dariusz; Szpinda, Michał; Mila-Kierzenkowska, Celestyna; Woźniak, Bartosz

    2013-01-01

    The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II). Blood was taken once in Control I and 4 times (every month) in Control II. In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively. Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I. In Control II, the similar differences as compared to Control I were observed throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is accompanied by oxidative stress. A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.

  20. A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion.

    PubMed Central

    Barrett, J; Dhurandhar, H N; Miller, E; Litwin, M S

    1975-01-01

    Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur. Images Fig. 1. Fig. 2. Fig. 3. PMID:242282

  1. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air-blood barrier model.

    PubMed

    Kasper, Jennifer Y; Feiden, Lisa; Hermanns, Maria I; Bantz, Christoph; Maskos, Michael; Unger, Ronald E; Kirkpatrick, C James

    2015-01-01

    The air-blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air-blood barrier, they impinge on the alveolar surfactant layer (10-20 nm in thickness) that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs) using in vitro mono- and complex coculture models of the air-blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate) of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release). At a distinct concentration (100 µg/mL) aSNP-plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP-NH2 caused a slight toxic effect, whereas aSNP-COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP-plain revealed an increased cytotoxicity in monocultures of A549, aSNP-NH2 caused a slightly augmented toxic effect, whereas aSNP-COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity) for aSNP-plain in combination with lung surfactant. However, a significant augmented IL-8 release was observed, but no

  2. Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in pulmonary embolism before and after treatment: preliminary results.

    PubMed

    Nagayama, Hiroki; Sueyoshi, Eijun; Hayashida, Takeshi; Ashizawa, Kazuto; Sakamoto, Ichiro; Uetani, Masataka

    2013-01-01

    The purpose was to investigate the quantification of lung perfusion blood volume (PBV) by dual-energy computed tomography (CT) in patients with pulmonary embolism (PE) before and after treatment. Twenty-five patients with PE underwent dual-energy CT angiography before and after treatment. In all 25 patients, pulmonary CT confirmed that there was no PE after treatment. This preliminary study demonstrated the possibility that quantification of lung PBV may reflect parenchymal arterial perfusion before and after treatment, including the compensatory increase of lung perfusion.

  3. Characterization of Microvesicles Released from Human Red Blood Cells.

    PubMed

    Nguyen, Duc Bach; Ly, Thi Bich Thuy; Wesseling, Mauro Carlos; Hittinger, Marius; Torge, Afra; Devitt, Andrew; Perrie, Yvonne; Bernhardt, Ingolf

    2016-01-01

    Extracellular vesicles (EVs) are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs) and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs) under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca2+ uptake and activation of protein kinase C. Experiments were performed based on single cell fluorescence imaging, fluorescence activated cell sorter/flow cytometer (FACS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The released MVs were collected by differential centrifugation and characterized in both their size and zeta potential. Treatment of RBCs with 4-bromo-A23187 (positive control), lysophosphatidic acid (LPA), or phorbol-12 myristate-13 acetate (PMA) in the presence of 2 mM extracellular Ca2+ led to an alteration of cell volume and cell morphology. In stimulated RBCs, exposure of phosphatidylserine (PS) and formation of MVs were observed by using annexin V-FITC. The shedding of MVs was also observed in the case of PMA treatment in the absence of Ca2+, especially under the transmitted bright field illumination. By using SEM, AFM and DLS the morphology and size of stimulated RBCs, MVs were characterized. The sizes of the two populations of MVs were 205.8 ± 51.4 nm and 125.6 ± 31.4 nm, respectively. Adhesion of stimulated RBCs and MVs was observed. The zeta potential of MVs was determined in the range from - 40 mV to - 10 mV depended on the solutions and buffers used. An

  4. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis.

    PubMed

    Pavord, Ian D; Lettis, Sally; Anzueto, Antonio; Barnes, Neil

    2016-09-01

    Inhaled corticosteroids are important in the management of chronic obstructive pulmonary disease (COPD), but can slightly increase the risk of pneumonia in patients with moderate-to-severe COPD. Patients with circulating eosinophil counts of 2% or more of blood leucocytes respond better to inhaled corticosteroids than do those with counts of less than 2% and it was therefore postulated that blood eosinophil count might also have an effect on the risk of pneumonia in patients with COPD. In this post-hoc meta-analysis, we investigate whether a 2% threshold can identify patients who differ in their risk of pneumonia, irrespective of inhaled corticosteroid treatment. From the GlaxoSmithKline trial registry, we selected randomised, double-blind, clinical trials of patients with COPD that had: inhaled corticosteroid arms (fluticasone propionate and salmeterol or fluticasone furoate and vilanterol); a control arm (not given inhaled fluticasone); and pre-randomisation measurements of blood eosinophil counts and were of at least 24 weeks in duration. With use of specified terms from the Medical Dictionary for Regulatory Activities we identified pneumonia adverse events in patient-level data. We calculated number of patients with pneumonia events, stratified by baseline blood eosinophil count (<2% vs ≥2% of blood leucocytes) and whether or not patients had received inhaled corticosteroids. We identified ten trials (conducted between 1998 and 2011), with eosinophil count data available for 10 861 patients with COPD. 4043 patients had baseline blood eosinophil counts of less than 2% and 6818 patients had baseline blood eosinophil counts of 2% or more. 149 (3·7%) patients with counts less than 2% had one or more pneumonia adverse events compared with 215 (3·2%) with counts of 2% or more (hazard ratio [HR] 1·31; 95% CI 1·06-1·62). In patients not treated with inhaled corticosteroids, 40 (3·8%) patients with less than 2% blood eosinophil counts had a pneumonia event

  5. Effect of Chemotherapy on Whole-Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in a Small Cohort of Patients with Pulmonary Tuberculosis▿†

    PubMed Central

    Bertholet, Sylvie; Horne, David J.; Laughlin, Elsa M.; Savlov, Margery; Tucakovic, Ines; Coler, Rhea N.; Narita, Masahiro; Reed, Steven G.

    2011-01-01

    The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to Mycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of M. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71 M. tuberculosis antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected M. tuberculosis proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients. PMID:21715581

  6. Effect of chemotherapy on whole-blood cytokine responses to Mycobacterium tuberculosis antigens in a small cohort of patients with pulmonary tuberculosis.

    PubMed

    Bertholet, Sylvie; Horne, David J; Laughlin, Elsa M; Savlov, Margery; Tucakovic, Ines; Coler, Rhea N; Narita, Masahiro; Reed, Steven G

    2011-08-01

    The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to Mycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of M. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71 M. tuberculosis antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected M. tuberculosis proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients.

  7. Genetic characterization of hantaviruses associated with sigmodontine rodents in an endemic area for hantavirus pulmonary syndrome in southern Brazil.

    PubMed

    de Oliveira, Renata Carvalho; Padula, Paula J; Gomes, Raphael; Martinez, Valeria P; Bellomo, Carla; Bonvicino, Cibele R; Freire e Lima, Danúbia Inês; Bragagnolo, Camila; Caldas, Antônio C S; D'Andrea, Paulo S; de Lemos, Elba R S

    2011-03-01

    An ecological assessment of reservoir species was conducted in a rural area (Jaborá) in the mid-west of the state of Santa Catarina in southern Brazil, where hantavirus pulmonary syndrome is endemic, to evaluate the prevalence of hantavirus infection in wild rodents. Blood and tissue samples were collected from 507 rodents during seven field trips from March 2004 to April 2006. Some of the animals were karyotyped to confirm morphological identification. Phylogenetic reconstructions of rodent specimens, based on the mitochondrial DNA cytochrome b gene sequences, were also obtained. Hantavirus antibody was found in 22 (4.3%) of the 507 rodents: 5 Akodon montensis, 2 Akodon paranaensis, 14 Oligoryzomys nigripes, and 1 Sooretamys angouya. Viral RNAs detected in O. nigripes and A. montensis were amplified and sequenced. O. nigripes virus genome was 97.5% (nt) and 98.4% (nt) identical to sequences published for Araucaria (Juquitiba-like) virus based on N and G2 fragment sequences. Viral sequences from A. montensis strain showed 89% and 88% nucleotide identities in a 905-nt fragment of the nucleocapsid (N) protein-coding region of the S segment when it was compared with two other Akodontine rodent-associated viruses from Paraguay, A. montensis and Akodon cursor, respectively. Phylogenetic analysis showed the cocirculation of two genetic hantavirus lineages in the state of Santa Catarina, one from O. nigripes and the other from A. montensis, previously characterized in Brazil and Paraguay, respectively. The hantavirus associated with A. montensis, designed Jaborá virus, represents a distinct phylogenetic lineage among the Brazilian hantaviruses.

  8. Repeatability and noise robustness of spicularity features for computer aided characterization of pulmonary nodules in CT

    NASA Astrophysics Data System (ADS)

    Wiemker, Rafael; Opfer, Roland; Bülow, Thomas; Kabus, Sven; Dharaiya, Ekta

    2008-03-01

    Computer aided characterization aims to support the differential diagnosis of indeterminate pulmonary nodules. A number of published studies have correlated automatically computed features from image processing with clinical diagnoses of malignancy vs. benignity. Often, however, a high number of features was trained on a relatively small number of diagnosed nodules, raising a certain skepticism as to how salient and numerically robust the various features really are. On the way towards computer aided diagnosis which is trusted in clinical practice, the credibility of the individual numerical features has to be carefully established. Nodule volume is the most crucial parameter for nodule characterization, and a number of studies are testing its repeatability. Apart from functional parameters (such as dynamic CT enhancement and PET uptake values), the next most widely used parameter is the surface characteristic (vascularization, spicularity, lobulation, smoothness). In this study, we test the repeatability of two simple surface smoothness features which can discriminate between smoothly delineated nodules and those with a high degree of surface irregularity. Robustness of the completely automatically computed features was tested with respect to the following aspects: (a) repeated CT scan of the same patient with equal dose, (b) repeated CT scan with much lower dose and much higher noise, (c) repeated automatic segmentation of the nodules using varying segmentation parameters, resulting in differing nodule surfaces. The tested nodules (81) were all solid or partially solid and included a high number of sub- and juxtapleural nodules. We found that both tested surface characterization features correlated reasonably well with each other (80%), and that in particular the mean-surface-shape-index showed an excellent repeatability: 98% correlation between equal dose CT scans, 93% between standard-dose and low-dose scan (without systematic shift), and 97% between varying HU

  9. A water-filled body plethysmograph for the measurement of pulmonary capillary blood flow during changes of intrathoracic pressure

    PubMed Central

    Kawakami, Yoshikazu; Menkes, Harold A.; DuBois, Arthur B.

    1970-01-01

    A water-filled body plethysmograph was constructed to measure gas exchange in man. As compared to an air-filled plethysmograph, its advantages were greater sensitivity, less thermal drift, and no change from adiabatic to isothermal conditions after a stepwise change of pressure. When five subjects were completely immersed within it and were breathing to the ambient atmosphere, they had a normal heart rate, oxygen consumption, CO2 output, and functional residual capacity. Pulmonary capillary blood flow ([unk]Qc) during and after Valsalva and Mueller maneuvers was calculated from measurements of N2O uptake. Control measurements of [unk]Qc were 2.58 liters/min per m2 at rest and 3.63 liters/min per m2 after moderate exercise. During the Valsalva maneuver at rest (intrapulmonary pressure: 24, SD 3.0, mm Hg), [unk]Qc decreased from a control of 2.58, SD 0.43, liters/min per m2 to 1.62, SD 0.26, liters/min per m2 with a decrease in pulmonary capillary stroke volume from a control of 42.4, SD 8.8, ml/stroke per m2 to 25.2, SD 5.5, ml/stroke per m2. After release of the Valsalva, there was an overshoot in [unk]Qc averaging +0.78, SD 0.41, liter/min per m2 accompanied by a significant increase in heart rate. Similar changes occurred during and after the Valsalva following moderate exercise. During the Mueller maneuver at rest and after exercise, [unk]Qc, heart rate, and central stroke volume did not change significantly. Images PMID:5422025

  10. Usefulness of Clinical Prediction Rules, D-dimer, and Arterial Blood Gas Analysis to Predict Pulmonary Embolism in Cancer Patients.

    PubMed

    Karamat, Asifa; Awan, Shazia; Hussain, Muhammad Ghazanfar; Al Hameed, Fahad; Butt, Faheem; Wahla, Ali Saeed

    2017-03-01

    Pulmonary embolism (PE) is seven times more common in cancer patients than non-cancer patients. Since the existing clinical prediction rules (CPRs) were validated predominantly in a non-cancer population, we decided to look at the utility of arterial blood gas (ABG) analysis and D-dimer in predicting PE in cancer patients. Electronic medical records were reviewed between December 2005 and November 2010. A total of 177 computed tomography pulmonary angiograms (CTPAs) were performed. We selected 104 individuals based on completeness of laboratory and clinical data. Patients were divided into two groups, CTPA positive (patients with PE) and CTPA negative (PE excluded). Wells score, Geneva score, and modified Geneva score were calculated for each patient. Primary outcomes of interest were the sensitivities, specificities, positive, and negative predictive values for all three CPRs. Of the total of 104 individuals who had CTPAs, 33 (31.7%) were positive for PE and 71 (68.3%) were negative. There was no difference in basic demographics between the two groups. Laboratory parameters were compared and partial pressure of oxygen was significantly lower in patients with PE (68.1 mmHg vs. 71 mmHg, p = 0.030). Clinical prediction rules showed good sensitivities (88-100%) and negative predictive values (93-100%). An alveolar-arterial (A-a) gradient > 20 had 100% sensitivity and negative predictive values. CPRs and a low A-a gradient were useful in excluding PE in cancer patients. There is a need for prospective trials to validate these results.

  11. The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review.

    PubMed

    Schuetz, Philipp; Marlowe, Robert J; Mueller, Beat

    2015-03-01

    Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

  12. [Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac preload in critically ill patients].

    PubMed

    Tomicic, Vinko; Graf, Jerónimo; Echevarría, Ghislaine; Espinoza, Mauricio; Abarca, Juan; Montes, José Miguel; Torres, Javier; Núñez, Gastón; Guerrero, Julia; Luppi, Mario; Canals, Claudio

    2005-06-01

    Monitoring of cardiac preload by determination of pulmonary artery occlusion pressure (PAOP) has been traditionally used to guide fluid therapy to optimize cardiac output (CO). Since factors such as intrathoracic pressure and ventricular compliance may modify PAOP, volumetric estimators of preload have been developed. The PiCCO system is able to measure CO and intrathoracic blood volume (ITBV) by transpulmonary thermodilution. To compare a volumetric (ITBV) versus a pressure (PAOP) determination to accurately estimate cardiac preload in severely ill patients. From June 2001 to October 2003, 22 mechanically ventilated patients with hemodynamic instability underwent hemodynamic monitoring with pulmonary artery catheter (PAC) and PiCCO system. ITBV index (ITBVI), PAOP and CI were measured simultaneously by both methods. One hundred thirty eight deltas (D) were obtained from the difference of ITBVI, PAOP, CI-PAC and CI-PiCCO between 6-12 am and 6-12 pm. Linear regression analysis of DITBVI versus Eth CI-PiCCO and Eth PAOP versus DCI-PAC were made. Mean age of patients was 60.8 +/- 19.4 years. APACHE II was 23.9 +/- 7. Fifteen patients met criteria for acute respiratory distress syndrome (ARDS). Delta ITBVI significantly correlated with DCI-PiCCO (r=0.54; 95% confidence interval = 0.41-0.65; p <0.01). There was no correlation between DPAOP and DCI-PAC. ITBVI correlated better with CI than PAOP, and therefore it seems to be a more accurate estimator of preload in unstable, mechanically ventilated patients.

  13. Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism

    PubMed Central

    Egermayer, P.; Town, G; Turner, J.; Heaton, D.; Mee, A.; Beard, M.

    1998-01-01

    BACKGROUND—A study was undertaken to assess the usefulness of the SimpliRED D-dimer test, arterial oxygen tension, and respiratory rate measurement for excluding pulmonary embolism (PE) and venous thromboembolism (VTE).
METHODS—Lung scans were performed in 517 consecutive medical inpatients with suspected acute PE over a one year period. Predetermined end points for objectively diagnosed PE in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary angiogram, (3) a high probability ventilation perfusion lung scan when the pretest probability was also high, and (4) the unanimous opinion of an adjudication committee. Deep vein thrombosis (DVT) was diagnosed by standard ultrasound and venography.
RESULTS—A total of 40 cases of PE and 37 cases of DVT were objectively diagnosed. The predictive value of a negative SimpliRED test for excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO2 of ⩾80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory rate of ⩽20/min was 0.95 (error rate 14/308). The best combination of findings for excluding PE was a negative SimpliRED test and PaO2⩾80 mm Hg, which gave a predictive value of 1.0 (error rate 0/93). The predictive value of a negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249).
CONCLUSIONS—All three of these observations are helpful in excluding PE. When any two parameters were normal, PE was very unlikely. In patients with a negative SimpliRED test and PaO2 of ⩾80 mm Hg a lung scan is usually unnecessary. Application of this approach for triage in the preliminary assessment of suspected PE could lead to a reduced rate of false positive diagnoses and considerable resource savings.

 PMID:10193368

  14. Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

    PubMed

    Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

    2017-02-01

    Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

  15. Effect of gravitational overloads, hypokinesia and hypodynamia on the vessels of the pulmonary blood circuit

    NASA Technical Reports Server (NTRS)

    Kasimtsev, A. A.

    1980-01-01

    Vessels of the pulmonary circuit are studied under normal conditions, in exposure to single stress or continuous threshold endurable chestspine gravitational stresses, and one to eight weak hypokinesia and hypodynamic effects followed by stress. Examination methods include rentgenography and microrentgenography, clearing, and histology. In exposure to gravitational stress the distal portions of the arterial vessels of the 3 and 4 orders constrict, while all veins dilate. Sinuosity of all vessels is noted. The volume of the capillary bed increases and signs of perivascular edema occur. Due to hypokinesia and hypodynamia the arteries constricted and the arterial bed becomes poor. The veins of all orders dilate and the volume of the capillary bed increases. The changes grew greater the longer the terms of hypodyamic effects. Successive combination of hypokinesia and hypodynamia and gravitational stresses cause more pronounced changes than separate effects of these two factors and result in great deformity of the vascular walls, including their rupture and penetration of formed elements beyond the limits of the vascular bed.

  16. A fatal case of Nocardia otitidiscaviarum pulmonary infection and brain abscess: taxonomic characterization by molecular techniques

    PubMed Central

    Pelaez, Ana Isabel; del Mar Garcia-Suarez, Maria; Manteca, Angel; Melon, Ovidio; Aranaz, Carlos; Cimadevilla, Rafael; Mendez, Francisco Javier; Vazquez, Fernando

    2009-01-01

    We report on a rare case of pulmonary Nocardiosis and brain abscess caused by Nocardia otitidiscaviarum in an elderly woman with chronic obstructive pulmonary disease. Taxonomic identification involved phenotypic testing, restriction fragment length polymorphism (RFLP), and complete 16S rRNA gene sequencing. PMID:19366439

  17. A fatal case of Nocardia otitidiscaviarum pulmonary infection and brain abscess: taxonomic characterization by molecular techniques.

    PubMed

    Pelaez, Ana Isabel; Garcia-Suarez, Maria del Mar; Manteca, Angel; Melon, Ovidio; Aranaz, Carlos; Cimadevilla, Rafael; Mendez, Francisco Javier; Vazquez, Fernando

    2009-04-14

    We report on a rare case of pulmonary Nocardiosis and brain abscess caused by Nocardia otitidiscaviarum in an elderly woman with chronic obstructive pulmonary disease. Taxonomic identification involved phenotypic testing, restriction fragment length polymorphism (RFLP), and complete 16S rRNA gene sequencing.

  18. The relative distribution of pulmocutaneous blood flow in Rana catesbeiana: effects of pulmonary or cutaneous hypoxia.

    PubMed

    Boutilier, R G; Glass, M L; Heisler, N

    1986-11-01

    The distribution of pulmocutaneous heart output to lungs and skin was determined in non-anaesthetized, fully recovered bullfrogs (Rana catesbeiana) by application of the microsphere method in order to study the modulation of blood flow to different gas exchange sites in amphibians during environmental air and water hypoxia. The relative perfusion of various skin areas was found to be rather heterogeneously distributed with an over-proportionately high blood flow to the ventral body surface. This distribution of flow among different skin areas remained unaffected by any type of environmental hypoxia. The relative perfusion of lungs and skin, however, was significantly affected by the pattern of environmental oxygen partial pressure. The relative lung perfusion (approximately equal to 80% of pulmocutaneous flow in normoxic control conditions) was increased during water hypoxia, and reduced with lowered inspired PO2. This mechanism could be interpreted as a readjustment of blood flow towards the gas exchange site with higher oxygen partial pressure, but may also represent a mechanism to prevent oxygen loss from the body stores at gas exchange sites of low oxygen tension.

  19. Quantitative photoacoustic characterization of blood clot in blood: A mechanobiological assessment through spectral information

    NASA Astrophysics Data System (ADS)

    Biswas, Deblina; Vasudevan, Srivathsan; Chen, George C. K.; Sharma, Norman

    2017-02-01

    Formation of blood clots, called thrombus, can happen due to hyper-coagulation of blood. Thrombi, while moving through blood vessels can impede blood flow, an important criterion for many critical diseases like deep vein thrombosis and heart attacks. Understanding mechanical properties of clot formation is vital for assessment of severity of thrombosis and proper treatment. However, biomechanics of thrombus is less known to clinicians and not very well investigated. Photoacoustic (PA) spectral response, a non-invasive technique, is proposed to investigate the mechanism of formation of blood clots through elasticity and also differentiate clots from blood. Distinct shift (increase in frequency) of the PA response dominant frequency during clot formation is reported. In addition, quantitative differentiation of blood clots from blood has been achieved through parameters like dominant frequency and spectral energy of PA spectral response. Nearly twofold increases in dominant frequency in blood clots compared to blood were found in the PA spectral response. Significant changes in energy also help in quantitatively differentiating clots from blood, in the blood. Our results reveal that increase in density during clot formation is reflected in the PA spectral response, a significant step towards understanding the mechanobiology of thrombus formation. Hence, the proposed tool, in addition to detecting thrombus formation, could reveal mechanical properties of the sample through quantitative photoacoustic spectral parameters.

  20. Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions

    PubMed Central

    Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun

    2017-01-01

    This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*. PMID:28225064

  1. Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions.

    PubMed

    Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun

    2017-02-22

    This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*.

  2. Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder.

    PubMed

    Cai, Xingshi; Yang, Yang; Xie, Xiangyang; Yu, Fanglin; Yang, Yanfang; Yang, Zhenbo; Zhang, Tao; Mei, Xingguo

    2016-07-01

    This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery.

  3. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors.

    PubMed

    Voortman, Johannes; Lee, Jih-Hsiang; Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Lucchi, Marco; Smith, William I; Meltzer, Paul; Wang, Yisong; Giaccone, Giuseppe

    2010-07-20

    The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

  4. Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease.

    PubMed

    Kim, Deog Kyeom; Cho, Michael H; Hersh, Craig P; Lomas, David A; Miller, Bruce E; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H; Crapo, James D; Riley, John H; Tal-Singer, Ruth; Silverman, Edwin K

    2012-12-15

    A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10(-8)), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009-0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

  5. Characterization of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension From REVEAL

    PubMed Central

    Liu, Juliana; Parsons, Lori; Hassoun, Paul M.; McGoon, Michael; Badesch, David B.; Miller, Dave P.; Nicolls, Mark R.; Zamanian, Roham T.

    2010-01-01

    Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco

  6. Characterization of the postjunctional α2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins

    PubMed Central

    Görnemann, T; von Wenckstern, H; Kleuser, B; Villalón, C M; Centurión, D; Jähnichen, S; Pertz, H H

    2007-01-01

    Background and purpose: In terms of postjunctional α2-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the α2-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. Experimental approach: α-adrenoceptor-mediated vasoconstriction was studied using a tissue bath protocol. mRNA profile and relative quantification of α2-adrenoceptor subtypes were determined in porcine pulmonary veins using reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Key results: In porcine pulmonary veins, noradrenaline, phenylephrine (α1-adrenoceptor agonist), UK14304 and clonidine (α2-adrenoceptor agonists) caused concentration-dependent contractions. The rank order of agonist potency was: NA≈UK14304≈clonidine > phenylephrine. UK14304 responses were antagonised by MK912 (noncompetitive antagonist parameter pD'2: 10.1), rauwolscine (pKB: 9.5), yohimbine (pKB: 9.1), WB4101 (pKB: 8.7), ARC239 (pKB: 7.5), prazosin (pKB: 7.1) and BRL44408 (pKB: 7.0). Antagonist potencies fitted best with radioligand binding data (pKi) at the human recombinant α2C-adrenoceptor (r2 = 0.96, P = 0.0001). Correlation with α2B-adrenoceptors was lower (r2 = 0.74, P > 0.01) and no correlation was obtained with α2A-adrenoceptors. Moreover, RT-PCR studies in porcine pulmonary veins showed mRNA signals for α2A- and α2C-adrenoceptors, but not for α2B-adrenoceptors, whilst real-time PCR studies indicated a prominent expression of α2C-adrenoceptor mRNA. Conclusions and Implications: Postjunctional α2C-adrenoceptors mediated contraction in porcine pulmonary veins. α1-Adrenoceptors also seem to be present in this tissue. Since α2-adrenoceptor responsiveness is increased when pulmonary vascular tone is elevated, α2C-adrenoceptor antagonists may be beneficial in diseases such as pulmonary hypertension or congestive heart failure. PMID:17375080

  7. Dielectrophoretic characterization of erythrocytes: positive ABO blood types.

    PubMed

    Srivastava, Soumya K; Daggolu, Prashant R; Burgess, Shane C; Minerick, Adrienne R

    2008-12-01

    Dielectrophoretic manipulation of erythrocytes/red blood cells is investigated as a tool to identify blood type for medical diagnostic applications. Positive blood types of the ABO typing system (A+, B+, AB+ and O+) were tested and cell responses quantified. The dielectrophoretic response of each blood type was observed in a platinum electrode microdevice, delivering a field of 0.025V(pp)/microm at 1 MHz. Responses were recorded via video microscopy for 120 s and erythrocyte positions were tabulated at 20-30 s intervals. Both vertical and horizontal motions of erythrocytes were quantified via image object recognition, object tracking in MATLAB, binning into appropriate electric field contoured regions (wedges) and statistical analysis. Cells of O+ type showed relatively attenuated response to the dielectrophoretic field and were distinguished with greater than 95% confidence from all the other three blood types. AB+ cell responses differed from A+ and B+ blood types likely because AB+ erythrocytes express both the A and B glycoforms on their membrane. This research suggests that dielectrophoresis of untreated erythrocytes beyond simple dilution depends on blood type and could be used in portable blood typing devices.

  8. "Data characterizing microfabricated human blood vessels created via hydrodynamic focusing".

    PubMed

    DiVito, Kyle A; Daniele, Michael A; Roberts, Steven A; Ligler, Frances S; Adams, André A

    2017-10-01

    This data article provides further detailed information related to our research article titled "Microfabricated Blood Vessels Undergo Neovascularization" (DiVito et al., 2017) [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF). Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into 'bullseye-like" cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016) [2], [3], [4], [5], [6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.

  9. Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

    PubMed

    Wang, W; Erf, G F; Wideman, R F

    2002-11-01

    Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which

  10. Development and Characterization of an Inducible Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

    PubMed

    Arias-Loza, Paula-Anahi; Jung, Pius; Abeßer, Marco; Umbenhauer, Sandra; Williams, Tatjana; Frantz, Stefan; Schuh, Kai; Pelzer, Theo

    2016-05-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality of life but also causes significant morbidity and mortality. The treatment of choice is pulmonary endarterectomy. However numerous patients do not qualify for pulmonary endarterectomy or present with residual vasculopathy post pulmonary endarterectomy and require specific vasodilator treatment. Currently, there is no available specific small animal model of CTEPH that could serve as tool to identify targetable molecular pathways and to test new treatment options. Thus, we generated and standardized a rat model that not only resembles functional and histological features of CTEPH but also emulates thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail vein injections of fibrinogen/collagen-covered polystyrene microspheres combined with thrombin and administered to 10-week-old male Wistar rats. After the third embolism, rats developed characteristic features of CTEPH including elevated right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy, pulmonary artery remodeling, increased serum brain natriuretic peptide levels, thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The current animal model seems suitable for detailed study of CTEPH pathophysiology and permits preclinical testing of new pharmacological therapies against CTEPH.

  11. Pretreatment neutrophil-to-lymphocyte ratio in peripheral blood was associated with pulmonary tuberculosis retreatment

    PubMed Central

    Yin, Yongmei; Kuai, Shougang; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Huang, Qiusheng

    2016-01-01

    Introduction The neutrophil-to-lymphocyte ratio (NLR) is a readily available biomarker associated with recurrence and survival in various diseases. The objective of this study was to investigate the relationship between NLR and pulmonary tuberculosis (PTB) retreatment. Material and methods This was a case-control study that included 306 newly diagnosed cases of PTB in the clinical database of the Infectious Hospital of Wuxi from December 2009 to December 2011. Of the 306 patients, a total of 68 cases were followed up with TB retreatment. The remaining 238 PTB patients who completed anti-TB treatment and were cured without retreatment were selected as controls. Results According to the ROC curve, the best cut-off value of NLR was 2.53, with a sensitivity of 70.6% and a specificity of 45.4%. The NLR ≥ 2.53 before anti-TB treatment was associated with PTB retreatment (OR = 1.994, 95% CI: 1.116–3.564; adjusted OR (AOR) = 2.409, 95% CI: 1.212–4.788). The retreatment rates with NLR ≥ 2.53 and NLR < 2.53 were 27.1% and 15.5%, respectively, with a significant difference (log-rank test; p = 0.010). Additionally, cavitation on chest X-ray (OR = 2.922, 95% CI: 1.654–5.411; AOR = 2.482, 95% CI: 1.230–5.007), history of smoking (OR = 2.202, 95% CI: 1.158–3.493; AOR = 2.321, 95% CI: 1.135–4.745) and age ≥ 60 (OR = 3.828, 95% CI: 1.626–9.015; AOR = 2.931, 95% CI: 1.122–7.653) were also associated with PTB retreatment. Conclusions NLR ≥ 2.53 is predictive of PTB retreatment. Otherwise, initial cavitation on chest X-ray, history of smoking, and age of ≥ 60 are also risk factors for PTB retreatment. PMID:28261295

  12. Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

    2012-01-01

    Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID

  13. Single-breath breath-holding estimate of pulmonary blood flow in man: comparison with direct Fick cardiac output.

    PubMed

    Kendrick, A H; Rozkovec, A; Papouchado, M; West, J; Laszlo, G

    1989-06-01

    1. Resting pulmonary blood flow (Q), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding (Qc) and compared with direct Fick cardiac output (Qf) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Qc estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Qc in the patients and in six normal subjects. 3. Qc tended to overestimate Qf, the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Qc in the patients was 0.75 l/min and in the normal subjects was 0.66 l/min. For Qf it was 0.72 l/min. There was no significant difference in Qc measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q, monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.

  14. Expression of inducible cell adhesion molecules in the normal human lung: immunohistochemical study of their distribution in pulmonary blood vessels.

    PubMed

    Feuerhake, F; Füchsl, G; Bals, R; Welsch, U

    1998-10-01

    The distribution of cell adhesion molecules in the normal human lung was investigated using antibodies to E-selectin, P-selectin, intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Lectin staining by Ulex europaeus type I agglutinin (UEA I) and immunohistochemistry for von Willebrand factor (vWF) was used to visualize a maximum of blood vessels per section. In the bronchial mucosa, staining for P-selectin was positive in ca 90%, and staining for E-selectin, VCAM-1, and ICAM-1 was positive in 40-70% of the vessels stained with UEA I. In the pulmonary circulation (vasa publica) ca 90% of non-capillary vessels stained by anti-vWF expressed P-selectin, 54% VCAM-1, 41% E-selectin, and only ca 20% ICAM 1. The alveolar capillaries were stained consistently by UEA I, but not by the panel of antibodies tested. The alveolar epithelium and, inconstantly, basal cells of the bronchial epithelium were positive for ICAM-1. The distribution pattern of inducible adhesion molecules in normal human lung tissue suggests that a permanent low-grade endothelial activation may exist in particular in the mucosa of the airways, which could be due to the normal antigen exposure via inhaled air.

  15. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    SciTech Connect

    Singh, Anurag K. . E-mail: singan@mail.nih.gov; Karimpour, Shervin E.; Savani, Bipin N.; Guion, Peter M.S.; Hope, Andrew J.; Mansueti, John R.; Ning, Holly; Altemus, Rosemary M. Ph.D.; Wu, Colin O.; Barrett, A. John

    2006-10-01

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV{sub 1}) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

  16. Intrathoracic splenosis: a rare false-positive cause of somatostatin imaging in characterization of solitary pulmonary nodule.

    PubMed

    Mahmoudian, Babak; Javadrashid, Reza; Fakhrjoo, Ashraf

    2015-02-01

    Scanning using a somatostatin receptor analog such as Tc-EDDA/HYNIC-TOC has sensitivity and specificity similar to those of FDG-PET, which has high accuracy in the characterization of a solitary pulmonary nodule (SPN). We describe a 63-year-old man with well-defined SPN in the left lung on chest x-ray and CT scan. Whole-body scanning and chest SPECT were performed with Tc-EDDA/HYNIC-TOC for the characterization of SPN. Abnormal focal increased radiotracer uptake in the left hemithorax was detected. In addition, no spleen activity was observed in the anatomical location. Cytopathologic evaluation of SPN revealed splenosis.

  17. Reproducibility of pulmonary blood flow measurements by phase-contrast MRI using different 1.5 T MR scanners at two institutions

    PubMed Central

    Iraha, Rin; Tsuchiya, Nanae; Yamashiro, Tsuneo; Iwasawa, Tae

    2017-01-01

    Background Magnetic resonance imaging (MRI) can be beneficial for diagnosis of disease by offering quantitative information. However, reproducibility can be a major problem when there is a numerical threshold in multi-institution, multi-vendor situations. Purpose To measure pulmonary blood flow with phase-contrast (PC) imaging using two different MR scanners (1.5 T) at different institutions in the same participants and to examine the reproducibility of the measurements. Material and Methods Participants were 10 healthy volunteers (5 men; age range, 27–36 years). The measurements included the mean and maximal blood velocities, the mean blood flow volume, and the acceleration time and volume (AT and AV), derived from the time-flow curve of the PC-MRI. Simultaneously obtained maximal, minimal, and mean areas from regions of interest set in the pulmonary artery were also calculated. In order to calculate the reproducibility of the quantitative variables, intra-class correlation coefficients (ICCs) were employed. When an adequate ICC was obtained, Bland–Altman analysis was conducted to identify any systematic bias. Results The ICCs were almost perfect for the mean blood flow volume and the AV (r = 0.82 and 0.80), and were substantial in the mean and maximal areas, and the AT (r = 0.63, 0.74, and 0.64, respectively). However, there was a fixed bias in the area measurement between the two scanners. Also, the AV had a proportional bias. Conclusion Our results reveal that various indices derived from PC-MRI on different MR scanners are promising as common indices for pulmonary flow assessment. Research and clinical use of PC-MRI for the pulmonary artery is expected to extend to multi-institution situations. PMID:28210495

  18. Characterization of an epizootic of pulmonary edema in swine associated with fumonisin in corn screenings.

    PubMed

    Osweiler, G D; Ross, P F; Wilson, T M; Nelson, P E; Witte, S T; Carson, T L; Rice, L G; Nelson, H A

    1992-01-01

    In 1989, corn screenings were associated with acute interstitial pulmonary edema, hydrothorax, and death in swine. Attack rate was 5-50%, case fatality rate was 50-90%, and clinical course was 1-2 days. Screenings from farms with pigs affected with pulmonary edema contained 20-330 micrograms fumonisin B1 per gram. Screenings containing 92 micrograms fumonisin B1 per gram fed to weanling pigs caused pulmonary edema and death. Sterilized corn inoculated with Fusarium moniliforme and diluted 1:1 with clean corn contained fumonisin B1 (17 micrograms/g) and caused acute pulmonary edema when fed for 5 days. Survivors developed subacute hepatotoxicosis with individual hepatocellular necrosis, hepatomegalocytosis, and increased numbers of mitotic figures. Similar liver lesions occurred in pigs given fumonisin B1 intravenously at 0.8 mg/kg body weight for 14 days.

  19. Dissociation between the time courses of femoral artery blood flow and pulmonary VO2 during repeated bouts of heavy knee extension exercise in humans.

    PubMed

    Fukuba, Yoshiyuki; Ohe, Yukie; Miura, Akira; Kitano, Asami; Endo, Masako; Sato, Hironori; Miyachi, Motohiko; Koga, Shunsaku; Fukuda, Osamu

    2004-05-01

    It has frequently been demonstrated that prior heavy cycling exercise facilitates pulmonary O(2) kinetics at the onset of subsequent heavy exercise. This might be due to improved muscle perfusion via acidosis-induced vasodilating effects. However, it is difficult to measure the blood flow (BF) to the working muscles (via the femoral artery) during cycling exercise. We therefore selected supine knee extension (KE) exercise as an alternative, and investigated whether the faster O(2) kinetics in the 2nd bout was matched by proportionally faster BF kinetics to the exercising muscle. Nine healthy subjects (aged 21-44 years) volunteered to participate in this study. The protocol consisted of two consecutive 6-min KE exercise bouts in a supine position (work rate: 70-75% of peak power) separated by a 6-min baseline rest (EX1 to EX2). During the protocol, a pulsed Doppler ultrasound technique was utilized to continuously measure the BF in the right femoral artery. The protocol was repeated at least 6 times to characterize the precise kinetics. In agreement with previous studies using cycling exercise, the O(2) kinetics in the 2nd bout were facilitated compared with that in the 1st bout [mean +/-s.d. of the 'effective' time constant (tau): EX1, 68.6 +/- 15.9, versus EX2, 58.0 +/- 14.4 s. Phase II-tau: EX1, 48.7 +/- 9.0, versus EX2, 41.2 +/- 13.3 s. Empirical index of the slow component (Delta O(2(6-3))): EX1, 78 +/- 44, versus EX2, 57 +/- 36 ml min(-1) (P < 0.05)]. However, no substantial difference was observed for the facilitation of the femoral artery BF response to the 1st and 2nd exercise bouts [i.e. the 'effective'tau of the femoral artery BF: EX1, 40.8 +/- 16.9, versus EX2, 39.0 +/- 17.1 s (P > 0.05)]. It was concluded that the faster pulmonary O(2) kinetics during heavy KE exercise following prior heavy exercise was not associated with a similar modulation in the BF to the working muscles.

  20. The effect of supine exercise on the distribution of regional pulmonary blood flow measured using proton MRI

    PubMed Central

    Hall, E. T.; Sá, R. C.; Holverda, S.; Arai, T. J.; Dubowitz, D. J.; Theilmann, R. J.; Prisk, G. K.

    2013-01-01

    The Zone model of pulmonary perfusion predicts that exercise reduces perfusion heterogeneity because increased vascular pressure redistributes flow to gravitationally nondependent lung, and causes dilation and recruitment of blood vessels. However, during exercise in animals, perfusion heterogeneity as measured by the relative dispersion (RD, SD/mean) is not significantly decreased. We evaluated the effect of exercise on pulmonary perfusion in six healthy supine humans using magnetic resonance imaging (MRI). Data were acquired at rest, while exercising (∼27% of maximal oxygen consumption) using a MRI-compatible ergometer, and in recovery. Images were acquired in most of the right lung in the sagittal plane at functional residual capacity, using a 1.5-T MR scanner equipped with a torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and regional proton density using a fast multiecho gradient-echo sequence. Perfusion images were corrected for coil-based signal heterogeneity, large conduit vessels removed and quantified (in ml·min−1·ml−1) (perfusion), and also normalized for density and quantified (in ml·min−1·g−1) (density-normalized perfusion, DNP) accounting for tissue redistribution. DNP increased during exercise (11.1 ± 3.5 rest, 18.8 ± 2.3 exercise, 13.2 ± 2.2 recovery, ml·min−1·g−1, P < 0.0001), and the increase was largest in nondependent lung (110 ± 61% increase in nondependent, 63 ± 35% in mid, 70 ± 33% in dependent, P < 0.005). The RD of perfusion decreased with exercise (0.93 ± 0.21 rest, 0.73 ± 0.13 exercise, 0.94 ± 0.18 recovery, P < 0.005). The RD of DNP showed a similar trend (0.82 ± 0.14 rest, 0.75 ± 0.09 exercise, 0.81 ± 0.10 recovery, P = 0.13). In conclusion, in contrast to animal studies, in supine humans, mild exercise decreased perfusion heterogeneity, consistent with Zone model predictions. PMID:24356515

  1. In vitro characterization and pharmacokinetics in mice following pulmonary delivery of itraconazole as cyclodextrin solubilized solution.

    PubMed

    Yang, Wei; Chow, Keat Theng; Lang, Bo; Wiederhold, Nathan P; Johnston, Keith P; Williams, Robert O

    2010-03-18

    This study aims to make a 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) solubilized itraconazole (ITZ) solution (i.e., HPbetaCD-ITZ) suitable for pulmonary delivery by nebulization, and compare pharmacokinetics of inhaled nebulized aerosols of HPbetaCD-ITZ versus a colloidal dispersion of ITZ nanoparticulate formulation (i.e., URF-ITZ). Solid state characterizations of lyophilized HPbetaCD-ITZ by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated the formation of dynamic inclusion complexes between ITZ and HPbetaCD. Nebulized aerosols of both HPbetaCD-ITZ and colloidal dispersion of URF-ITZ were confirmed suitable for deep lung delivery. Single doses of the nebulized aerosols (equivalent to 5.3mg ITZ/mL in 5 mL) in mice produced similar ITZ lung depositions and pharmacokinetic profiles, with ITZ lung levels of approximately 4 microg/g wet lung weight upon completion of nebulization and remained above 0.5 microg/g at 24h. HPbetaCD-ITZ demonstrated faster systemic absorption of ITZ across lung epithelium than URF-ITZ, with t(max) values of 1.5 and 3.0 h, and AUC(0-infinity) of 2513 and 3717 ng h/mL, respectively. The fast absorption of solubilized ITZ across lung mucosal surface may be due in part to the elimination of the phase-to-phase transition. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Formulation, Characterization and Pulmonary Deposition of Nebulized Celecoxib Encapsulated Nanostructured Lipid Carriers

    PubMed Central

    Patlolla, Ram R.; Chougule, Mahavir; Patel, Apurva R.; Jackson, Tanise; Tata, Prasad NV; Singh, Mandip

    2010-01-01

    The aim of the current study was to encapsulate celecoxib (Cxb) in the Nanostructured Lipid Carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in vitro aersolization of Cxb-NLC formulation showed FPF of 75.6 ± 4.6 %, MMAD of 1.6 ±0.13 μm and GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUCt/D in lung tissues compared to Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 L/h) compared to Cxb-Soln (20.03 L/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals. PMID:20153385

  3. A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry Aspergillus fumigatus Conidia

    PubMed Central

    Buskirk, Amanda D.; Green, Brett J.; Lemons, Angela R.; Nayak, Ajay P.; Goldsmith, W. Travis; Kashon, Michael L.; Anderson, Stacey E.; Hettick, Justin M.; Templeton, Steven P.; Germolec, Dori R.; Beezhold, Donald H.

    2014-01-01

    Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Δalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1×105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Δalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants. PMID:25340353

  4. Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

    PubMed Central

    Huang, Huichang; Yang, Rui; Yao, Lan

    2017-01-01

    Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays. A PCR array was used to further test the same samples. Two additional groups of patients were recruited according to the same criteria with healthy control(HC) recruited as well and subjected to peripheral blood mononuclear cell isolation (PBMC)and analysis of TCF-7, β-catenin, cyclin D2, IFN-γ, and tumor necrosis factor (TNF)-α expression in CD14- cells (lymphocytes) and CD14+ cells by quantitative PCR. The changes of expression of β-catenin, CD69+ and IFN-γ by CD3+, CD14- and CD14+ cells in vitro with stimulation of LiCl were tested by flow cytometry. Whole genome oligo microarrays showed a significant decrease in expression of the Wnt signaling pathway in severe PTB patients. Further analysis of the Wnt pathway by PCR array indicated that TCF-7, β-catenin, and cyclin D2 expression was significantly reduced in severe PTB patients compared with mild PTB patients. In the additionally recruited patients, TCF-7, β-catenin, and cyclin D2 were expressed in both CD14+ and CD14- cells, while β-catenin was decreased significantly in CD14- cells compared with CD14+ cells in severe PTB patients, and IFN-γ and TNF-α expression in CD14- cells was also reduced significantly in severe PTB patients. β-catenin can directly trigger T cell activation and IFN-γsecretion in PBMCs stimulated for 24 hours. These findings indicate that Wnt pathway and its key genes, such as β-catenin, were impaired in blood cells of patients with

  5. Pulmonary O2 uptake and leg blood flow kinetics during moderate exercise are slowed by hyperventilation-induced hypocapnic alkalosis

    PubMed Central

    Chin, Lisa M. K.; Heigenhauser, George J. F.; Paterson, Donald H.

    2010-01-01

    The effect of hyperventilation-induced hypocapnic alkalosis (Hypo) on the adjustment of pulmonary O2 uptake (V̇o2p) and leg femoral conduit artery (“bulk”) blood flow (LBF) during moderate-intensity exercise (Mod) was examined in eight young male adults. Subjects completed four to six repetitions of alternate-leg knee-extension exercise during normal breathing [Con; end-tidal partial pressure of CO2 (PetCO2) ∼40 mmHg] and sustained hyperventilation (Hypo; PetCO2 ∼20 mmHg). Increases in work rate were made instantaneously from baseline (3 W) to Mod (80% estimated lactate threshold). V̇o2p was measured breath by breath by mass spectrometry and volume turbine, and LBF (calculated from mean femoral artery blood velocity and femoral artery diameter) was measured simultaneously by Doppler ultrasound. Concentration changes of deoxy (Δ[HHb])-, oxy (Δ[O2Hb])-, and total hemoglobin-myoglobin (Δ[HbTot]) of the vastus lateralis muscle were measured continuously by near-infrared spectroscopy (NIRS). The kinetics of V̇o2p, LBF, and Δ[HHb] were modeled using a monoexponential equation by nonlinear regression. The time constants for the phase 2 V̇o2p (Hypo, 49 ± 26 s; Con, 28 ± 8 s) and LBF (Hypo, 46 ± 16 s; Con, 23 ± 6 s) were greater (P < 0.05) in Hypo compared with Con. However, the mean response time for the overall Δ[HHb] response was not different between conditions (Hypo, 23 ± 5 s; Con, 24 ± 3 s), whereas the Δ[HHb] amplitude was greater (P < 0.05) in Hypo (8.05 ± 7.47 a.u.) compared with Con (6.69 ± 6.31 a.u.). Combined, these results suggest that hyperventilation-induced hypocapnic alkalosis is associated with slower convective (i.e., slowed femoral artery and microvascular blood flow) and diffusive (i.e., greater fractional O2 extraction for a given ΔV̇o2p) O2 delivery, which may contribute to the hyperventilation-induced slowing of V̇o2p (and muscle O2 utilization) kinetics. PMID:20339012

  6. [Blood destruction in pulmonary alveoli: signs of vitality and determination of survival time].

    PubMed

    Oehmichen, M

    1984-01-01

    Lungs from 26 cases were examined in which blood was present as a result of a gunshot wound, a stab wound, or aspiration. Signs of vitality and of a time-dependent reaction sequence were evaluated to determine survival time. Only those morphologic criteria were considered that could be obtained on paraffin sections. In addition to H & E staining, siderin was identified with the Prussian blue reaction and the activities were determined of tartrate-resistant acid phosphatase, as macrophage marker, and naphthol AS-D chloracetate esterase, as granulocyte marker. The following criteria were evaluated: granulocyte emigration, erythrocyte adherence to the surface of macrophages, macrophage ingestion of erythrocytes, and determination of siderin as indicator of intracellular erythrocyte digestion. Adherence was also observed in those cases that did not survive. The initial sign of vitality was granulocyte emigration, which was observed for the first time after a survival time of 5 min. Erythrophages were found after a survival time of 30 min at least, siderophages after 17 h at the earliest. Literature dealing with vitality and age determination, as well as the pathogenesis of the reaction sequence, is discussed.

  7. Characterization of thermoplastic microfiltration chip for the separation of blood plasma from human blood.

    PubMed

    Chen, Pin-Chuan; Chen, Chih-Chun; Young, Kung-Chia

    2016-09-01

    In this study, we developed a fully thermoplastic microfiltration chip for the separation of blood plasma from human blood. Spiral microchannels were manufactured on a PMMA substrate using a micromilling machine, and a commercial polycarbonate membrane was bonded between two thermoplastic substrates. To achieve an excellent bonding between the commercial membrane and the thermoplastic substrates, we used a two-step injection and curing procedure of UV adhesive into a ring-shaped structure around the microchannel to efficiently prevent leakage during blood filtration. We performed multiple filtration experiments using human blood to compare the influence of three factors on separation efficiency: hematocrit level (40%, 23.2%, and 10.9%), membrane pore size (5 μm, 2 μm, and 1 μm), and flow rate (0.02 ml/min, 0.06 ml/min, 0.1 ml/min). To prevent hemolysis, the pressure within the microchannel was kept below 0.5 bars throughout all filtration experiments. The experimental results clearly demonstrated the following: (1) The proposed microfiltration chip is able to separate white blood cells and red blood cells from whole human blood with a separation efficiency that exceeds 95%; (2) no leakage occurred during any of the experiments, thereby demonstrating the effectiveness of bonding a commercial membrane with a thermoplastic substrate using UV adhesive in a ring-shaped structure; (3) separation efficiency can be increased by using a membrane with smaller pore size, by using diluted blood with lower hematocrit, or by injecting blood into the microfiltration chip at a lower flow rate.

  8. Ultrasonic Measurement of Fluid Viscosity for Blood Characterization

    NASA Astrophysics Data System (ADS)

    Nitta, Naotaka; Homma, Kazuhiro

    2005-06-01

    Although plaque rupture in arteriosclerosis is affected by not only its strength but also by hemodynamic factors, such as blood pressure and shear stress, in particular, the viscous coefficient which directly controls the magnitude of shear stress might be a risk factor in plaque rupture. Therefore, if the viscous coefficient can be assessed noninvasively, it can be a useful index for prediction of a plaque rupture and assessment of various diseases. In this work, an ultrasonic methodology to estimate the viscous coefficient was investigated by numerical simulation and flow-phantom experiment as the fundamental investigation for noninvasively assessing the viscous characteristics of blood. These results show that the proposed method is useful for estimating the kinematic viscosity coefficient in the viscous evaluation of blood.

  9. Genetic characterization of the ABO blood group in Neandertals

    PubMed Central

    2008-01-01

    Background The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence. PMID:19108732

  10. Characterization of Blood Flow in Capillaries by Numerical Simulation

    NASA Astrophysics Data System (ADS)

    Wang, Tong; Xing, Zhongwen

    2011-03-01

    We presents a numerical investigation of the axisymmetric, pressure driven motion of single file erythrocyte (i.e., red blood cell) suspensions flowing in capillaries of diameter 8- 11 μ m. The governing Navier-Stokes equations are discretized using the operator splitting technique and solved by the finite element method. The study takes consideration the particulate nature of the blood. The red blood cell (RBC) is modeled as a closed membrane filled with a Newtonian fluid which has the same viscosity as the surrounding plasma. The cell membrane is described by a spring model so that the deformability of the cells can be considered. An immersed boundary method is also developed for dealing with the cell/fluid interaction in the flow. Our study successfully recreates several important in vivo hemodynamic and hemorheological properties of microscopic blood flow, such as parachute shape of the cells, blunt velocity profile, and the Fahraeus effect, and they have been shown to have strong dependence on cell deformability, hematocrit and vessel size.

  11. Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma.

    PubMed

    Jujo, Takayuki; Sakao, Seiichiro; Kantake, Masashi; Maruoka, Miki; Tanabe, Nobuhiro; Kasahara, Yasunori; Kurosu, Katsushi; Masuda, Masahisa; Harigaya, Kenichi; Tatsumi, Koichiro

    2012-08-01

    In general, intravascular thrombus formation in the pulmonary arteries is considered to be the most common cause of chronic thromboembolic pulmonary hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like cells in endarterectomized tissues has been demonstrated. At the 2nd passage of these myofibroblast-like cells, a pleomorphic cell type was isolated. Pulmonary intimal sarcoma is a very uncommon neoplastic tumor thought to originate from subendothelial-mesenchymal cells of the pulmonary vascular wall. Because these pleomorphic cells were isolated from the pulmonary vascular beds, it is believed that the analysis of these cells may contribute to the understanding of pulmonary intimal sarcoma. We isolated cells from the endarterectomized tissue from patients with CTEPH and identified one type as sarcoma-like cells (SCLs). The SCLs were characterized as hyperproliferative, anchorage-independent, invasive and serum-independent. Moreover, C.B-17/lcr-scid/scidJcl mice injected subcutaneously with SCLs developed solid, undifferentiated tumors at the site of injection, and those injected intravenously with SCLs via the tail vein developed tumors which grew along the intimal surface of the pulmonary vessels, thus, demonstrating the high tumorigenic potential of these cells. The behavior of SCLs indicated that these cells may have a vascular cell-like potential which can affiliate them with the intimal surface of the pulmonary artery, and which may be shared with pulmonary intimal sarcoma. A further investigation of this mouse model with SCLs may elucidate the mechanism(s) underlying the development of pulmonary intimal sarcoma.

  12. Severity assessment of pulmonary embolism using dual energy CT - correlation of a pulmonary perfusion defect score with clinical and morphological parameters of blood oxygenation and right ventricular failure.

    PubMed

    Thieme, Sven F; Ashoori, Nima; Bamberg, Fabian; Sommer, Wieland H; Johnson, Thorsten R C; Leuchte, Hanno; Becker, Alexander; Maxien, Daniel; Helck, Andreas D; Behr, Jürgen; Reiser, Maximilian F; Nikolaou, Konstantin

    2012-02-01

    To correlate a Dual Energy (DE)-based visual perfusion defect scoring system with established CT-based and clinical parameters of pulmonary embolism (PE) severity. In 63 PE patients, DE perfusion maps were visually scored for perfusion defects (P-score). Vascular obstruction was quantified using the Mastora score. Both scores were correlated with short-axis diameters of the right and left ventricle, their ratio (RV/LV ratio), width of the pulmonary trunk, a number of clinical parameters and each other. Univariate and multivariate analyses were performed. Times to generate both scores were recorded. After univariate and multivariate analysis, a significant (p < 0.05) correlation with the P-score was shown for the Mastora score (r = 0.65), RV/LV ratio (r = 0.47), width of the pulmonary trunk (r = 0.26), troponin I (r = 0.43) and PaO(2) (r = -0.50). For the left ventricular diameter, only univariate analysis showed a significant correlation. Mastora score correlated significantly with RV/LV ratio (r = 0.36), width of the pulmonary trunk (r = 0.27), PaO(2) (r = -0.41) and troponin I (r = 0.37). Mean time for generating the P-score was significantly shorter than for the Mastora score. A DE-based P-score correlates with a number of parameters of PE severity. It might be easier and faster to perform than some traditional CT scoring methods for vascular obstruction.

  13. Expression of suppressor of cytokine signaling 1 in the peripheral blood of patients with idiopathic pulmonary fibrosis.

    PubMed

    Bao, Zhiyao; Zhang, Qiurui; Wan, Huanying; He, Ping; Zhou, Xin; Zhou, Min

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse parenchymal disease with a poor prognosis. A variety of cytokines and chemokines are involved in its pathophysiology. The aim of this study was to evaluate the clinical features in IPF patients with the expression of suppressor of cytokine signaling 1 (SOCS-1), which acts as a negative regulator of cytokine signaling. IPF patients (n = 20) and healthy controls (n = 16) were included in this study. The expression of SOCS-1 was analyzed in peripheral blood mononuclear cells (PBMC) of subjects using RT-PCR. Interleukin 4 (IL-4), transforming growth factor β1 (TGF-β1) and type I collagen expression were also analyzed in each individual using enzyme-linked immunosorbent assay (ELISA). The clinical characteristics of IPF patients were delineated. These results were analyzed by SPSS13.0 statistics software. SOCS-1 mRNA expression was significantly decreased in the PBMC of IPF patients compared with healthy controls; serum levels of IL-4 and TGF-β1 were higher in IPF patients. The patients with lower expression of SOCS-1 developed lower percentage of forced vital capacity (FVC%) and DLCO/VA. A patients' SOCS-1 mRNA level was negatively correlated with serum levels of IL-4, and negatively correlated with their high-resolution computed tomography (HRCT) scores. SOCS-1 mRNA can be detected in PBMC, and it is down-regulated in IPF patients. The expression of SOCS-1 is associated with the severity of IPF patients' symptoms, so it might be the predictor of disease severity. SOCS-1 might play an important role in IPF by reducing the expression of the T helper type 2 (Th2) cell-related cytokine IL-4.

  14. Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats

    PubMed Central

    Van Etten, Els W. M.; Stearne-Cullen, Lorna E. T.; Ten Kate, Marian T.; Bakker-Woudenberg, Irma A. J. M.

    2000-01-01

    The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after Aspergillus fumigatus inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with A. fumigatus and in reducing the dissemination of A. fumigatus to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection. PMID:10681315

  15. Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis.

    PubMed

    Ampel, Neil M; Nesbit, Lance A; Nguyen, Chinh T; Chavez, Suzette; Knox, Kenneth S; Johnson, Suzanne M; Pappagianis, Demosthenes

    2015-08-01

    The outcome of coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal disseminated coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active coccidioidomycosis (for both, P < 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all, P < 0.05). The cytokine profile among patients with active coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

    USDA-ARS?s Scientific Manuscript database

    Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

  17. States of low pulmonary blood flow can be detected non-invasively at the bedside measuring alveolar dead space.

    PubMed

    Tusman, Gerardo; Suarez-Sipmann, Fernando; Paez, Gabriel; Alvarez, Jorge; Bohm, Stephan H

    2012-06-01

    We tested whether the ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) can detect states of low pulmonary blood flow (PBF) in a non-invasive way. Fifteen patients undergoing cardiovascular surgeries with cardiopulmonary bypass (CPB) were studied. CPB is a technique that excludes the lungs from the general circulation. The weaning of CPB is a model that manipulates PBF in vivo because each time blood flow through the CPB decreases, expected PBF (ePBF) increases. Patients were liberated from CPB in steps of 20 % every 2' starting from 100 % CPB (very low ePBF) to 0 % CPB (100 % ePBF). During constant ventilation, volumetric capnograms were recorded and Bohr's dead space ratio (VD(Bohr)/VT), VD(alv)/VT(alv) and the ratio of airway dead space to tidal volume (VD(aw)/VT) were calculated. Before CPB, VD(Bohr)/VT was 0.36 ± 0.05, VD(aw)/VT 0.21 ± 0.04 and VD(alv)/VT(alv) 0.18 ± 0.06 (mean ± SD). During weaning from CPB, VD(aw)/VT remained unchanged while VD(Bohr)/VT and VD(alv)/VT(alv) decreased with increasing ePBF. At CPB of 80, 60, 40 and 20 % VD(Bohr)/VT was 0.64 ± 0.06, 0.55 ± 0.06, 0.47 ± 0.05 and 0.40 ± 0.04, respectively; p < 0.001 and VD(alv)/VT(alv) 0.53 ± 0.07, 0.40 ± 0.07, 0.29 ± 0.06 and 0.25 ± 0.04, respectively; p < 0.001). After CPB, VD(Bohr)/VT and VD(alv)/VT(alv) reached values similar to baseline (0.37 ± 0.04 and 0.19 ± 0.06, respectively). At constant ventilation the alveolar component of VD(Bohr)/VT increased in proportion to the deficit in lung perfusion.

  18. Radionuclide analysis of pulmonary blood volume: the response to spontaneous angina pectoris and sublingual nitroglycerin in patients with coronary artery disease.

    PubMed

    Slutsky, R; Mancini, G B; Costello, D; Hooper, W; Verba, J; Nelson, T; Shabetai, R; LeWinter, M M

    1983-02-01

    By manually assigning pulmonary regions of interest and deriving pulmonary time-activity (volume) curves, we were able to make count estimates of pulmonary blood volume (PBV) from gated cardiac blood pool scans. Five patients with coronary heart disease developed angina spontaneously while under a gamma camera. This produced an increase in cardiac volumes (p less than 0.05), a reduction in left ventricular ejection fraction (p less than 0.01), along with a marked increase in PBV (0.010 +/- 0.003 to 0.015 +/- 0.002 units, p less than 0.05). Nitroglycerin was then administered and reduced PBV in association with a return to normal in cardiac systolic function and size. In patients with stable chronic ischemic heart disease, sublingual nitroglycerin also reduced PBV (p less than 0.05), although not as much as when administered during an anginal episode. We conclude that gated imaging of the chest can be utilized to follow changes in PBV serially. These changes can be utilized to evaluate clinically important changes in hemodynamic status and the response to pharmacologic interventions.

  19. Characterization of Blood Properties from Coagulating Blood of Different Hematocrits Using Ultrasonic Backscatter and Attenuation

    NASA Astrophysics Data System (ADS)

    Huang, Chih-Chung; Wang, Shyh-Hau

    2006-09-01

    The influence of hematocrit on the change of blood properties during coagulating was extensively investigated using ultrasonic integrated backscatter and attenuation. Measurements were performed with porcine blood at hematocrits ranging from 25 to 55% using a 10 MHz transducer. Results showed that both integrated backscatter and attenuation are able to sensitively differentiate various stages of blood properties during coagulating. The slopes of integrated backscatter (Sr, dB/S) and attenuation (αr, dB\\cdotcm-1\\cdotMHz-1\\cdotmS-1) are increased relative to hematocrit. The best fits for Sr and αr as a function of hematocrit (H) equal to Sr=0.0357+1.62e-0.108H and αr=0.0281+0.003H, respectively. Variations of clotting time (Ts) and reaction time (Tα), estimated respectively from ultrasonic integrated backscatter and attenuation, associated with clot formation are also increased with hematocrit. This study demonstrates that blood hematocrit is a substantial factor affecting viscosity and backscattering properties of blood during coagulation capable of being discerned by ultrasonic backscattering and attenuation.

  20. [Effect of dragon's blood on TGF-beta/smads signal transduction molecule mRNA expression in the lung tissue of rats with pulmonary fibrosis].

    PubMed

    Nie, Li; Zheng, Bi-xia; Cheng, De-yun; Yang, Li-teng; Mu, Mao; Hu, Xiao-bo; Fang, Xun

    2007-09-01

    To investigate the effect of Dragon's Blood on the expression of TGF-beta signal transduction molecule TGFbetaR II or Smad4 mRNA in the lung tissue of rats with pulmonary fibrosis, and to evaluate the effect and its mechanism of Dragon's Blood on pulmonary fibrosis. 30 SD rats were randomly divided into three groups: fibrosis model, treatment and normal control groups. In model group and treatment group, the pulmonary fibrous tissues were induced to form with the intratracheal injection of bleomycin (5 mg/kg). In normal control group, saline was given intratracheally. Dragon's Blood was administered intragastricly in treatment group with a dose of 180 mg/kg diluted in 2 mL saline while saline was given intragastricly to other two groups with same volume from day 2 till day 28 after modeling. All rats were sacrificed on the 29th day. The rat lung histopathology was examined with HE staining. In situ hybridization was used to detect the expressions of TGFbetaR II and Smad4 mRNAs in lung tissue, and the expression of collagen fibril I was examined by an immunohistochemical staining. The inflammation cell counting in treatment group (12913.78 +/- 5640.12) was significant lower than that in model group (22243.60 +/- 5011.55, P < 0.01). The expression of pulmonary TGF/betaR II mRNA in treatment group was significant lower than that in model group (P < 0.01). In the Smad4 mRNA expression of lung tissue, there was no significant difference occurring between treatment group and model group (P > 0.05). The expression of collagen fibril I in the lung tissue of rats in treatment group was significant lower than that in model group (P < 0. 01). Dragon's Blood can effectively reduce rats' pulmonary fibrosis, of which the mechanisms may be to inhibit the expression of TGFbetaR II mRNA in the lung tissue and thus to have the preventive effect on the excessive deposit of collagen fibril I.

  1. [Cardiopulmonary exercise testing in chronic obstructive pulmonary disease (COPD) - breath-functional characterization and disease severity assessment].

    PubMed

    Mühle, A; Obst, A; Winkler, J; Ewert, R

    2015-09-01

    COPD is a heterogeneous disease with a wide range of clinical phenotypes and breath-functional dysfunctions. Cardiopulmonary exercise testing (CPET) allows describing all component parts of breathing and determining exercise capacity and the mechanisms of exercise limitation. From these aspects 64 COPD patient stages II, III and IV according to the conventional GOLD classification were examined by means of CPET to evaluate whether CPET can provide a better functional characterization of COPD than the standard investigation procedures in pulmonary practice.We could show that in pulmonary practice CPET is safely and effectively practicable in stable COPD patients of all GOLD stages. This method allowed a clinical and prognostic disease severity assessment of all patients, proving important differences of peak oxygen uptake in each GOLD stage, so that patients in spite of identical GOLD disease severity were to be assigned to different prognostic groups according CPET criteria. Furthermore, we found relevant differences of individual breath-functional patterns in exercise, which can neither be objectified nor be prognosticated by standard investigation procedures at rest.Therefore CPET allows, aside from an objective clinical and prognostic disease severity assessment, also a breath-functional evaluation in a subtly way in COPD patients reflecting the multidimensional background of the disease with variable dysfunctions in pulmonary ventilation, gas exchange, circulation and muscular function as well as associated cardio vascular comorbidities. The breath-functional phenotyping of the COPD patient seems to be meaningful in particular for an individualised therapy management.

  2. Blood

    MedlinePlus

    ... The liquid part, called plasma, is made of water, salts, and protein. Over half of your blood is plasma. The solid part of your blood contains red blood cells, white blood cells, and platelets. Red ...

  3. How Is Pulmonary Embolism Treated?

    MedlinePlus

    ... Twitter. How Is Pulmonary Embolism Treated? Pulmonary embolism (PE) is treated with medicines, procedures, and other therapies. The main goals of treating PE are to stop the blood clot from getting ...

  4. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

    PubMed Central

    2014-01-01

    Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for

  5. Assessment of quantitative polymerase chain reaction for equine herpesvirus-5 in blood, nasal secretions and bronchoalveolar lavage fluid for the laboratory diagnosis of equine multinodular pulmonary fibrosis.

    PubMed

    Pusterla, N; Magdesian, K G; Mapes, S M; Zavodovskaya, R; Kass, P H

    2017-01-01

    The ante mortem diagnosis of equine multinodular pulmonary fibrosis (EMPF) relies on histopathological results and polymerase chain reaction (PCR)-positive equine herpesvirus (EHV)-5 testing of lung tissue. Polymerase chain reaction detection of EHV-5 in bronchoalveolar lavage fluid (BALF) is commonly used to support a diagnosis of EMPF. However, the diagnostic power of EHV-5 testing on BALF and other biological samples such as blood and nasal secretions has yet to be shown to support a diagnosis of EMPF. To determine the frequency of detection and the viral loads of EHV-5 by quantitative PCR (qPCR) in blood, nasal secretions and BALF from horses confirmed with EMPF, healthy horses and horses with non-EMPF pulmonary diseases. Prospective study. The study population consisted of 70 adult horses divided into 4 groups based on a combination of clinical findings, cytology of BALF, imaging studies of the thoracic cavity and histopathology of pulmonary tissue: control group (n = 14), EMPF group (n = 11); inflammatory airway disease group (n = 32); and non-EMPF interstitial lung disease group (n = 13). For each horse, whole blood, nasal secretions and BALF were available for EHV-5 qPCR testing. Sensitivities, specificities and their respective 95% confidence intervals were calculated for viral loads from blood, nasal secretions and BALF. In addition, these measures were calculated for combined use of blood and nasal secretions. The detection of EHV-5 in BALF was strongly associated with EMPF (sensitivity 91%, specificity 98.3%). Detection of EHV-5 in blood was, independent of the viral loads, strongly associated with EMPF with a sensitivity of 91% and specificity of 83.1%. The detection of EHV-5 in nasal secretions displayed the highest sensitivity (72.7%) and specificity (83.1%) at a level of >245,890 glycoprotein B target genes/million cells to support a diagnosis of EMPF. Dually positive blood and nasal secretions at any viral loads in support of EMPF yielded a

  6. IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

    EPA Science Inventory

    Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

  7. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

    USDA-ARS?s Scientific Manuscript database

    Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

  8. IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

    EPA Science Inventory

    Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

  9. High-resolution CT in simple coal workers' pneumoconiosis. Lack of correlation with pulmonary function tests and arterial blood gas values

    SciTech Connect

    Collins, L.C.; Willing, S.; Bretz, R.; Harty, M.; Lane, E.; Anderson, W.H. )

    1993-10-01

    We examined 21 miners by means of standard chest radiography, high-resolution computerized tomography (HRCT), pulmonary function tests, and resting arterial blood gas levels. Using the ILO/UC classification of pneumoconiosis, 7 miners had category 1/0 or 2/1 simple coal workers' pneumoconiosis (CWP). By HRCT, nodules were identified in 12 miners; 4 of 9 were classified as category 0/0 CWP; 2 of 5, 0/1 CWP; 5 of 6, 1/0 CWP; and 1 of 1, 2/1 CWP by chest radiograph. Focal emphysema was identified by HRCT in 7 miners; 4 of 9 were classified as 0/0 CWP; 2 of 5, 0/1 CWP; and 1 of 6, 1/0 CWP by standard chest radiography. Four miners with definite nodules confirmed by HRCT had focal emphysema, while three without nodules had focal emphysema. Pulmonary function testing was not different between miners with or without CWP by standard chest radiography, nor was it different between miners with or without definite nodules evidenced by HRCT. No difference in resting oxygenation was found between any group of miners. The presence of focal emphysema confirmed by HRCT did not significantly affect pulmonary function tests on resting arterial blood gas values. There was, however, a significantly lower FEV1 and mean forced expiratory flow during the middle half of forced vital capacity with lifetime nonsmoking miners. The presence of CWP on chest radiography was significantly correlated with smoking cigarettes but not the years of mining. The presence of nodules on HRCT approached a significant correlation with cigarette smoking, but focal emphysema did not. For detecting evidence of coal dust accumulation in lung parenchyma and identifying focal emphysema, HRCT was more sensitive than standard chest radiography. However, despite earlier detection of parenchymal abnormalities, abnormal pulmonary function attributable to coal dust could not be identified.

  10. Intra- and inter-reader reproducibility of blood flow measurements on the ascending aorta and pulmonary artery using cardiac magnetic resonance.

    PubMed

    Di Leo, Giovanni; D'Angelo, Ida Daniela; Alì, Marco; Cannaò, Paola Maria; Mauri, Giovanni; Secchi, Francesco; Sardanelli, Francesco

    2017-03-01

    The aim of our study was to estimate the intra- and inter-reader reproducibility of blood flow measurements in the ascending aorta and main pulmonary artery using cardiac magnetic resonance (CMR) and a semi-automated segmentation method. The ethics committee approved this retrospective study. A total of 50 consecutive patients (35 males and 15 females; mean age±standard deviation 27±13 years) affected by congenital heart disease were reviewed. They underwent CMR for flow analysis of the ascending aorta and main pulmonary artery (1.5 T, through-plane phase-contrast sequences). Two independent readers (R1, trained radiology resident; R2, lower-trained technician student) obtained segmented images twice (>10-day interval), using a semi-automated method of segmentation. Peak velocity, forward and backward flows were obtained. Bland-Altman analysis was used and reproducibility was reported as complement to 100% of the ratio between the coefficient of repeatability and the mean. R1 intra-reader reproducibility for the aorta was 99% (peak velocity), 95% (forward flow) and 49% (backward flow); for the pulmonary artery, 99%, 91% and 90%, respectively. R2 intra-reader reproducibility was 92%, 91% and 38%; 98%, 86% and 87%, respectively. Inter-reader reproducibility for the aorta was 91%, 85% and 20%; for the pulmonary artery 96%, 75%, and 82%, respectively. Our results showed a good to excellent reproducibility of blood flow measurements of CMR together with a semiautomated method of segmentation, for all variables except the backward flow of the ascending aorta, with a limited impact of operator's training.

  11. Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

    PubMed

    Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

    2016-10-01

    The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy.

  12. Characterizing dynamic changes in the human blood transcriptional network.

    PubMed

    Zhu, Jun; Chen, Yanqing; Leonardson, Amy S; Wang, Kai; Lamb, John R; Emilsson, Valur; Schadt, Eric E

    2010-02-12

    Gene expression data generated systematically in a given system over multiple time points provides a source of perturbation that can be leveraged to infer causal relationships among genes explaining network changes. Previously, we showed that food intake has a large impact on blood gene expression patterns and that these responses, either in terms of gene expression level or gene-gene connectivity, are strongly associated with metabolic diseases. In this study, we explored which genes drive the changes of gene expression patterns in response to time and food intake. We applied the Granger causality test and the dynamic Bayesian network to gene expression data generated from blood samples collected at multiple time points during the course of a day. The simulation result shows that combining many short time series together is as powerful to infer Granger causality as using a single long time series. Using the Granger causality test, we identified genes that were supported as the most likely causal candidates for the coordinated temporal changes in the network. These results show that PER1 is a key regulator of the blood transcriptional network, in which multiple biological processes are under circadian rhythm regulation. The fasted and fed dynamic Bayesian networks showed that over 72% of dynamic connections are self links. Finally, we show that different processes such as inflammation and lipid metabolism, which are disconnected in the static network, become dynamically linked in response to food intake, which would suggest that increasing nutritional load leads to coordinate regulation of these biological processes. In conclusion, our results suggest that food intake has a profound impact on the dynamic co-regulation of multiple biological processes, such as metabolism, immune response, apoptosis and circadian rhythm. The results could have broader implications for the design of studies of disease association and drug response in clinical trials.

  13. Nanomechanical characterization of red blood cells using optical tweezers.

    PubMed

    Li, Chuan; Liu, K K

    2008-04-01

    Deformation behaviours of red blood cells (RBCs) have been studied by applying stretching forces via optical tweezers. Combined with finite-element analyses (FEA), the RBCs' mechanical properties are determined quantitatively based on a best fitting between the experimental deformed geometries and the simulated counterparts. Experimentally, a silica beads attached erythrocyte is optical-mechanically stretched to different lengths. On the theoretical front, a large deformation model with Mooney-Rivlin constitutive equations has been simulated by using FEA to predict the cell deformation geometries. The numerically simulated transverse and longitudinal strains which are in a good agreement with the experimental measurements facilitate the determination of elastic constants of the cells.

  14. Characterization of the pulmonary inflammatory response to an anaerobic bacterial challenge.

    PubMed

    Nelson, S; Laughon, B E; Summer, W R; Eckhaus, M A; Bartlett, J G; Jakab, G J

    1986-02-01

    Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung abscess. However, the pulmonary antibacterial response to these organisms has not been well described. To define this, mice were intratracheally inoculated with 10(9) Bacteroides gingivalis, a member of the B. melaninogenicus group, and a common clinical isolate from periodontal disease and anaerobic pulmonary infections. Studies after intratracheal challenge included bacteriologic and histopathologic examination, pulmonary cellular response, lactic dehydrogenase (LDH) and albumin levels in lung lavage fluid, and wet lung weight. Overall mortality was 25%. In the surviving animals, pulmonary lavage showed a marked recruitment of polymorphonuclear leukocytes that was associated with significant bacterial killing by 48 h. Histopathologic examination showed an acute, severe necrotizing bronchopneumonia. Pulmonary abscess formation occurred in 37% of animals. Severe parenchymal damage was further documented by a marked increase in LDH levels in lavage fluids. Mean LDH levels in lavage fluid increased to 850 +/- 25 units/first lavage at 24 h postchallenge compared with control values of 65 +/- 10 units/first lavage. Lung lavage also demonstrated an extensive influx of serum albumin consistent with injury to the alveolar capillary membrane. Albumin levels in lung lavage were highest at 24 h after intratracheal challenge (3.25 +/- 0.3 mg/first lavage), whereas lavage fluid from control mice had nondetectable albumin levels. Wet lung weights maximally increased from 0.12 +/- 0.01 g in control mice to 0.28 +/- 0.03 g 24 h after bacterial-challenge. These data demonstrate tht B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Paucicellular Fibrointimal Proliferation Characterizes Pediatric Pulmonary Vein Stenosis: Clinicopathologic Analysis of 213 Samples From 97 Patients.

    PubMed

    Kovach, Alexandra E; Magcalas, Philip M; Ireland, Christina; McEnany, Kerry; Oliveira, Andre M; Kieran, Mark W; Baird, Christopher W; Jenkins, Kathy; Vargas, Sara O

    2017-09-01

    Pulmonary vein stenosis (PVS) is a luminal narrowing of extrapulmonary pulmonary veins. In pediatric patients, it arises following repair of congenital heart disease, particularly anomalous pulmonary venous return; in lung disease, especially prematurity; and rarely in isolation. The etiology is unknown and the course often fatal without lung transplantation. We hypothesized that systematic clinicopathologic review of pediatric PVS could provide further pathogenic insight. We included patients who underwent first resection of pulmonary venous tissue for symptomatic PVS at our pediatric referral center from 1995 to 2014. Clinical records and hematoxylin and eosin slides were reviewed. Subsets were immunostained for smooth muscle actin, Ki-67, β-catenin, estrogen receptor, and other markers and analyzed for USP6 gene rearrangement. A total of 97 patients (57% male; median age: 6 mo) were identified. Overall, 59 (61%) had prior congenital heart disease repair, 35 involving pulmonary vein manipulation. Samples included 213 separate anatomic sites (median: 2/patient). Histologically, all showed sparsely cellular intimal expansion composed of haphazardly arranged fibroblasts with slender nuclei in myxoid matrix. This tissue merged with underlying collagen. Most samples had a variably continuous sheath of cardiomyocytes. Ancillary tests supported a reactive fibroblastic proliferation; in particular, fibroblasts showed cytoplasmic β-catenin localization, no estrogen receptor expression, and no USP6 rearrangement. At last follow-up (mean: 2.3 y), 46% of patients had died of disease. Pediatric PVS uniformly consists of a paucicellular fibrointimal proliferation, irrespective of clinical scenario. It may be best conceived of as a form of reactive hyperplasia. As with other forms of vascular remodeling, trauma (iatrogenic or occult) is likely an inciting factor. A comprehensive understanding of the surgical pathology of PVS may further inform therapeutic strategies in this

  16. Pulmonary embolism

    SciTech Connect

    Dunnick, N.R.; Newman, G.E.; Perlmutt, L.M.; Braun, S.D.

    1988-11-01

    Pulmonary embolism is a common medical problem whose incidence is likely to increase in our aging population. Although it is life-threatening, effective therapy exists. The treatment is not, however, without significant complications. Thus, accurate diagnosis is important. Unfortunately, the clinical manifestations of pulmonary embolism are nonspecific. Furthermore, in many patients the symptoms of an acute embolism are superimposed on underlying chronic heart or lung disease. Thus, a high index of suspicion is needed to identify pulmonary emboli. Laboratory parameters, including arterial oxygen tensions and electrocardiography, are as nonspecific as the clinical signs. They may be more useful in excluding another process than in diagnosing pulmonary embolism. The first radiologic examination is the chest radiograph, but the clinical symptoms are frequently out of proportion to the findings on the chest films. Classic manifestations of pulmonary embolism on the chest radiograph include a wedge-shaped peripheral opacity and a segmental or lobar diminution in vascularity with prominent central arteries. However, these findings are not commonly seen and, even when present, are not specific. Even less specific findings include cardiomegaly, pulmonary infiltrate, elevation of a hemidiaphragm, and pleural effusion. Many patients with pulmonary embolism may have a normal chest radiograph. The chest radiograph is essential, however, for two purposes. First, it may identify another cause of the patient's symptoms, such as a rib fracture, dissecting aortic aneurysm, or pneumothorax. Second, a chest radiograph is essential to interpretation of the radionuclide V/Q scan. The perfusion scan accurately reflects the perfusion of the lung. However, a perfusion defect may result from a variety of etiologies. Any process such as vascular stenosis or compression by tumor may restrict blood flow. 84 references.

  17. Total Anomalous Pulmonary Venous Connection (TAPVC)

    MedlinePlus

    ... affect the heart? In the right atrium, oxygen-rich (red) blood from the pulmonary veins mixes with ... affect the heart? In the right atrium, oxygen-rich (red) blood from the pulmonary veins mixes with ...

  18. Pulmonary Rehabilitation: MedlinePlus Health Topic

    MedlinePlus

    ... better in your daily life. NIH: National Heart, Lung, and Blood Institute Start Here Pulmonary Rehabilitation (American Thoracic Society) - PDF Pulmonary Rehabilitation (National Heart, Lung, and Blood Institute) What Are the Benefits and Risks of ...

  19. Characterization of differences between blood sample matrices in untargeted metabolomics.

    PubMed

    Denery, Judith R; Nunes, Ashlee A K; Dickerson, Tobin J

    2011-02-01

    Large-scale proteomic and metabolomic technologies are increasingly gaining attention for their use in the diagnosis of human disease. In order to ensure the statistical power of relevant markers, such analyses must incorporate a large number of representative samples. While in a best-case scenario these samples are collected through a study design that is specifically tailored for the desired analysis, often studies must rely upon the analysis of large numbers of previously banked samples that may or may not have complete and accurate documentation of their associated collection and storage methods. In this study, several human blood matrices were analyzed and compared for the quality of metabolomic output. The sample types that were tested include plasma prepared with a variety of anticoagulants and serum collected by venipuncture and capillary blood collection protocols. Analysis with liquid chromatography-mass spectrometry (LC-MS) revealed only subtle differences between the various plasma preparation methods. Differences between the serum and plasma samples appear to be largely peptide/protein-based and are consistent with the biological distinction of the two matrices. Interestingly, the small molecule lysophosphatidylinositol was found to be in higher abundance in plasma, as a possible consequence of the effect of the intrinsic clotting cascade on adjacent metabolic pathways. Comparison of the small-molecule profiles of the capillary- and venipuncture-collected samples revealed 23 statistically significant compound differences between these sample types. Most of these features can be attributed to surfactants and detergents used to pretreat the skin in order to maintain the sterility of sample collection. However, several have identical mass and molecular formulas as endogenous human metabolites and could be erroneously attributed to actual metabolic perturbations. Understanding the extent of these matrix effects is important for control of systematic bias

  20. Calculating alveolar capillary conductance and pulmonary capillary blood volume: comparing the multiple- and single-inspired oxygen tension methods

    PubMed Central

    Ceridon, Maile L.; Beck, Kenneth C.; Olson, Thomas P.; Bilezikian, Jordan A.

    2010-01-01

    Key elements for determining alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity (Dl) for carbon monoxide (DlCO) or for nitric oxide (DlNO) are the reaction rate of carbon monoxide with hemoglobin (θCO) and the DmCO/DlNO relationship (α-ratio). Although a range of values have been reported, currently there is no consensus regarding these parameters. The study purpose was to define optimal parameters (θCO, α-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2 tension [inspired fraction of O2 (FiO2)] method relative to the multiple-FiO2 method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2 and single-FiO2 methods (rebreathe technique) and were tabulated by applying previously reported θCO equations (both methods) and by varying the α-ratio (single-FiO2 method) from 1.90 to 2.50. Values were then compared between methods throughout the examined α-ratios. Dm and Vc were critically dependent on the applied θCO equation. For the multiple-FiO2 method, Dm was highly variable between θCO equations (rest and exercise); the range of Vc was less widespread. For the single-FiO2 method, the θCO equation by Reeves and Park (1992) combined with an α-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2 method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2 method (using DlCO and DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values. PMID:20538842

  1. [Effect of mucolytic therapy on the production of reactive oxygen species in the blood of patients with an exacerbation of chronic obstructive pulmonary disease].

    PubMed

    Farkhutdinov, U R; Farkhutdinov, R R; Petriakov, V V; Farkhutdinov, Sh U; Mirkhaĭdarov, A M

    2010-01-01

    To study the production of active oxygen forms (AOF) in the blood of patients with an exacerbation of chronic obstructive pulmonary disease (COPD) and the effect of the mycolytic agent Ambroxol on this process. Fifty-two patients with an exacerbation of COPD were examined. The patients were divided into 2 groups: 1) a study group (n = 25) received conventional therapy (antibiotics, bronchodilators, glucocorticosteroids) and Ambroxol inhalation; 2) a control group (n = 27) had conventional therapy and placebo (saline) inhalation. The blood production of AOF was studied by luminol-dependent chemiluminescence (CL) assay. The intensity of whole blood CL was increased in patients with COPD. Ambroxol therapy reduced blood AOF generation and improved clinical parameters. On the contrary, the high intensity of blood CL remained and a slowing trend in the symptoms of the disease was noted in the control group. The use of Ambroxol in COPD exacerbations corrected AOF production in the blood of the patients and enhanced the efficiency of their treatment.

  2. Characterization of the phase dependent pulmonary response following irritant inhalation exposure to nitrogen dioxide gas

    SciTech Connect

    Siegel, P.D.

    1988-01-01

    The present study utilized NO{sub 2} to fingerprint the biochemical reaction of the pulmonary compartment to oxidative damage and to correlate this with histopathology following acute and subacute exposures to NO{sub 2}. Acute exposure to NO{sub 2} produced dose-dependent immediate increases in the nonenzymatic parameters of pulmonary protein content, protease inhibitor activity and lung weight. The enzymatic activities of lactate dehydrogenase (LDH), choline kinase and beta-glucuronidase were elevated by two days following acute exposure. All of the above parameters were elevated following subacute exposure, however, nonenzymatic manifestations were attenuated with respect to enzymatic alterations. Hydroxyurea-induced granulocytopenia attenuated the increases in activities of LDH and beta-glucuronidase following acute, but not subacute exposures. Cycloheximide-induced protein synthesis inhibition decrease the LDH and beta-glucuronidase response to NO{sub 2} without altering the increases in protein content or protease inhibitor activity.

  3. Blood

    MedlinePlus

    ... that die or are lost from the body. White Blood Cells White blood cells (WBCs, and also ... of severe pain. previous continue Diseases of the White Blood Cells Neutropenia (pronounced: new-truh-PEE-nee- ...

  4. Inhaled nitric oxide alters the distribution of blood flow in the healthy human lung, suggesting active hypoxic pulmonary vasoconstriction in normoxia.

    PubMed

    Asadi, Amran K; Sá, Rui Carlos; Kim, Nick H; Theilmann, Rebecca J; Hopkins, Susan R; Buxton, Richard B; Prisk, G Kim

    2015-02-01

    Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2 ) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2 × iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2 , there were statistically significant increases in Global Fluctuation Dispersion, (a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2 dependent (P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia (P = 0.007) and normoxia (P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung. Copyright © 2015 the American Physiological Society.

  5. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis

    PubMed Central

    Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV

    2016-01-01

    Background: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. Materials and Methods: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively. The collected sputum samples were initially stained with Ziehl–Neelsen stain for confirmation of presence of tubercle Bacilli. Primary isolation was done on Sabouraud Dextrose Agar (SDA). The candidal colonies were confirmed microscopically for the presence of pseudohyphae. Further speciation of the positive candidal samples was carried out using ChromAgar. Result: The total fungal prevalence among 60 patients with pulmonary tuberculosis on SDA was 33 (55%) Candida and 3 (5%) Aspergillus. The prevalence of different candidal species on ChromAgar showed C. albicans as the predominant one, followed by Candida tropicalis and Candida krusei. Freshly diagnosed or untreated group was less commonly associated with pulmonary mycoses than chronic or treated group. The prevalence of Candida had increased with treatment, duration and age, and it was more in males than females. Conclusion: The present study confirms the phenomenon of opportunistic candidal infections in pulmonary tuberculosis patients. Rapid and reliable identification of Candida species is essential as they differ in their virulence and sensitivity to antifungal drugs. PMID:27601806

  6. Handbook of pulmonary emergencies

    SciTech Connect

    Spaquolo, S.V.; Medinger, A

    1986-01-01

    This book presents information on the following topics: clinical assessment of the patient with pulmonary disease; interpretation of arterial blood gases in the emergency patient; life-threatening pneumonia; extrapulmonic ventilatory failure; acute inhalation lung disease; pulmonary edema; near drowning; chest trauma; upper airway emergencies; chronic lung disease with acute respiratory decompensation; acute respiratory failure in the patient with chronic airflow obstruction; asthma; hemoptysis; embolic pulmonary disease; superior vena cava syndrome; catastrophic pleural disease; ventilatory assistance and its complications; and ventilator emergencies.

  7. Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study.

    PubMed

    Overbeek, Maria J; Groepenhoff, Herman; Voskuyl, Alexandre E; Smit, Egbert F; Peeters, Jochem W L; Vonk-Noordegraaf, Anton; Spreeuwenberg, Marieke D; Dijkmans, Ben C; Boonstra, Anco

    2008-10-01

    There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT. TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 +/- 7% vs. 63 +/- 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 +/- 6% vs. 39 +/- 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0-25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0-21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups. SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.

  8. Towards a multi-wavelength spectroscopy platform for blood characterization and analysis.

    PubMed

    Kisomi, Alireza Avakh; Landari, Hamza; Boukadoum, Mounir; Miled, Amine; Gosselin, Benoit

    2016-08-01

    Passing multiple light wavelengths through a blood sample makes it possible to investigate the presence and composition of cells, metabolytes and analytes such as blood cells, glucose, lactate and oxygen, providing valuable indications for diagnostic and health monitoring. In this paper, we present a test prototype of a multi-wavelength blood spectroscopy platform integrated with a microfluidic substrate to collect and convey blood samples through a series of micro-LEDs and a photo-detector. This spectroscopy platform is a proof of concept for a system that can collect absorbance and transmittance parameters of blood samples at several wavelengths within the visible and NIR spectrum, and transmit them wirelessly to a base station for real-time calculation and analysis. In-vitro measurements are performed with the proposed prototype with 5 channels covering wavelength from 400 nm to 940 nm A full characterization results of the proposed device are presented.

  9. Cross-sectional study on respiratory effect of toner-exposed work in manufacturing plants, Japan: pulmonary function, blood cells, and biochemical markers.

    PubMed

    Kitamura, H; Terunuma, N; Kurosaki, S; Hata, K; Ide, R; Kuga, H; Kakiuchi, N; Masuda, M; Totsuzaki, T; Osato, A; Uchino, B; Kitahara, K; Iwasaki, A; Yoshizumi, K; Morimoto, Y; Kasai, H; Murase, T; Higashi, T

    2009-06-01

    The aim of the study is to examine the relationship between toner-exposed work and health indices related to respiratory disorders and to confirm the baseline of a cohort study to clarify the effect of toner exposure in manufacturing plants. Subjects were 1614 male workers (809 toner-exposed workers and 805 referents) who were engaged in toner manufacturing plants in Japan (Fuji Xerox Co., Ltd). The age of subjects was from 19 to 59 years, and the average age was 40.2 years(median 40 years, SD 7.67). We conducted a pulmonary function test (PEFR, VC, FVC, FEV(1.0)%, V25/Ht) and a blood cell test (RBC, Hb, Hct, Plt, WBC, cell contents of WBC) and measured biochemical indices in blood (ALT, AST, gamma-GTP, CRP, IgE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Student t-test and logistic regression analysis were applied to compare between the toner-exposed workers and the referents and to analyze the relationship among indices of effects and independent factors. There was no significant difference between the two groups in blood cell count and biochemical indices. Inflammation- and allergy-related markers such as 8OHdG and IgE also showed no significant difference between toner-exposed workers and the referents. The influence of smoking on pulmonary function indices was observed, but there was no relationship between the pulmonary function and toner-exposed work. In this article, we report a preliminary cross-sectional analysis in the subjects of a cohort study. No difference in pulmonary function indices was observed between the toner-exposed workers and the referents, and there was no consistent relationship between the exposure status and examined indices; however, the prevalence of subjective respiratory symptoms was higher in the exposed workers as presented in another report. Further analysis is important in the ongoing cohort study to clarify the effect of toner exposure on respiratory systems.

  10. Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru

    PubMed Central

    Marcos, Luis A.; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Weil, Gary J.; Fischer, Peter U.

    2012-01-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers. PMID:22826497

  11. Histochemical analyses and quantum dot imaging of microvascular blood flow with pulmonary edema in living mouse lungs by "in vivo cryotechnique".

    PubMed

    Saitoh, Yurika; Terada, Nobuo; Saitoh, Sei; Ohno, Nobuhiko; Jin, Takashi; Ohno, Shinichi

    2012-02-01

    Light microscopic imaging of blood vessels and distribution of serum proteins is essential to analyze hemodynamics in living animal lungs under normal respiration or respiratory diseases. In this study, to demonstrate dynamically changing morphology and immunohistochemical images of their living states, "in vivo cryotechnique" (IVCT) combined with freeze-substitution fixation was applied to anesthetized mouse lungs. By hematoxylin-eosin staining, morphological features, such as shapes of alveolar septum and sizes of alveolar lumen, reflected their respiratory conditions in vivo, and alveolar capillaries were filled with variously shaped erythrocytes. Albumin was usually immunolocalized in the capillaries, which was confirmed by double-immunostaining for aquaporin-1 of endothelium. To capture accurate time-courses of blood flow in peripheral pulmonary alveoli, glutathione-coated quantum dots (QDs) were injected into right ventricles, and then IVCT was performed at different time-points after the QD injection. QDs were localized in most arterioles and some alveolar capillaries at 1 s, and later in venules at 2 s, reflecting a typical blood flow direction in vivo. Three-dimensional QD images of microvascular networks were reconstructed by confocal laser scanning microscopy. It was also applied to lungs of acute pulmonary hypertension mouse model. Erythrocytes were crammed in blood vessels, and some serum components leaked into alveolar lumens, as confirmed by mouse albumin immunostaining. Some separated collagen fibers and connecting elastic fibers were still detected in edematous tunica adventitia near terminal bronchioles. Thus, IVCT combined with histochemical approaches enabled us to capture native images of dynamically changing structures and microvascular hemodynamics of living mouse lungs.

  12. Cell surface alterations during blood-storage characterized by artificial aggregation of washed red blood cells.

    PubMed

    Hessel, E; Lerche, D

    1985-01-01

    Aggregation measurement of washed human erythrocytes (RBC) were carried out in a NaCl-PBS solution under laminar shear conditions. Artificial aggregation of fresh and stored erythrocytes was caused by decreased pH and reduced ionic strength and characterized by collision efficiency alpha. Generally, the collision efficiency alpha of stored erythrocytes rises with the increased storage time. Such an aggregation technique might be useful to detect and quantify changes of the membrane and/or the surface structure due to aging and/or storage.

  13. [Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

    PubMed

    Bokov, P; Delclaux, C

    2016-02-01

    Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint.

  14. Effect of blood pH on pulmonary artery pressure, left atrial pressure and fluid filtration rate in isolated rabbit lung.

    PubMed

    Pinto-Plata, V M; Pozo-Parilli, J C; Baum-Agay, A; Curiel, C; Sánchez de León, R

    1995-09-01

    To determine the effects of pH changes on Pulmonary Artery Pressure (PAP), 18 isolated rabbit lung preparations, perfused with autologous blood mixture and constant PaCO2 have been studied. Each preparation was studied under 3 conditions: Baseline: 30 minutes equilibration period. Acidosis: pH was decreased by 0.2 N HCl infusion, the ventilatory rate was changed and different CO2 mixtures were used to maintain the PCO2 within the initial parameters. Compensated Acidosis (CA): pH was returned to normal values by 0.7 N NaHCO3 infusion maintaining PCO2 in its initial values. The decrease in pH (acidosis) from 7.36 +/- 0.05 to 7.18 +/- 0.06 at constant PCO2, generated a significant increase in PAP (13.6 +/- 3.2 cm H2O to 18.8 +/- 5.2 cm H2O, p < 0.01). The pH increase (CA) from 7.18 +/- 0.06 to 7.40 +/- 0.09 caused the PAP to decrease (18.8 +/- 5.2 cm H2O to 15.9 +/- 4.2 cm H2O); the fluid filtration rate remained unchanged during the whole experiment. It is concluded that blood pH changes at constant PCO2 result in significant changes of PAP. Acidemia produces pulmonary vasoconstriction, which may be a contributing factor in the genesis of pulmonary hypertension in clinical conditions with increased hydrogen ion concentration [H+].

  15. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

    PubMed

    Iino, Nozomi; Matsunaga, Toshiyuki; Harada, Tsuyoshi; Igarashi, Seiji; Koyama, Iwao; Komoda, Tsugikazu

    2007-05-01

    Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

  16. Primary Pulmonary NUT-Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterization

    PubMed Central

    Sholl, Lynette M.; Nishino, Mizuki; Pokharel, Saraswati; Mino-Kenudson, Mari; French, Christopher A.; Janne, Pasi A.; Lathan, Christopher

    2015-01-01

    NUT midline carcinoma (NMC) is a poorly differentiated tumor typically driven by a t(15;19) rearrangement leading to a NUT fusion event. This rare and uniformly fatal tumor arises in multiple organ sites, however the clinical, radiographic, and pathologic characteristics of primary pulmonary NMC are poorly defined. We identified eight cases of primary pulmonary NMC in our consult practice over four years and, using a NUT immunohistochemistry screen, retrospectively identified one additional case from 166 (0.6%) consecutive in-house biopsies of lung carcinomas lacking glandular differentiation. Eight cases had available clinical and radiographic data and shared a remarkable degree of similarity. The median age at presentation was 30 (range 21-68). Six patients had little or no smoking history. All complained of one to three months of cough at presentation. Computed tomography scans showed a large, centrally-located primary mass with confluent involvement of mediastinal lymph nodes, pleural disease, and sparing of the contralateral lung. Lytic bone metastases were common but brain metastases were absent in all cases. Pathologically, all cases showed primitive-appearing round to epitheloid cells growing in nests and sheets. All tumors expressed keratin, p63 or p40, and NUT protein. Eight cases had a FISH-proven BRD4-NUT or BRD3-NUT rearrangement; one case was presumed to have a NUT-variant fusion event. Median overall survival was 2.2 months. Despite the rarity of primary pulmonary NMC, it is important to recognize this entity in order to counsel patients regarding outcome and to identify candidates for targeted BRD inhibitors currently in clinical trials. PMID:26001144

  17. Molecular characterization of the early B cell response to pulmonary Cryptococcus neoformans infection.

    PubMed

    Rohatgi, Soma; Pirofski, Liise-anne

    2012-12-15

    The role of B cells in host defense against fungi has been difficult to establish. We quantified and determined the molecular derivation of B-1a, B-1b, and B-2 B cell populations in C57BL/6 mice after pulmonary infection with Cryptococcus neoformans. Total B-1 and B-2 cell numbers increased in lungs and peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal expansion. Labeled capsular (24067) and acapsular (Cap67) C. neoformans strains were used to identify C. neoformans-binding B cell subsets by flow cytometry. Peritoneal cavity B-1a B cells exhibited the most acapsular and capsular C. neoformans binding in C. neoformans-infected mice, and C. neoformans-selected B-1 B cells secreted laminarin- and C. neoformans-binding IgM. Single-cell PCR-based sequence analysis of B-1a, B-1b, and B-2 cell IgH V region H chain (V(H)) genes revealed increased usage of V(H)11 and V(H)12, respectively, in acapsular and capsular C. neoformans-selected B-1a cells. Germline V(H) segments were used, with capsular C. neoformans-selected cells having less junctional diversity than acapsular C. neoformans-selected cells. Further studies in B-1 B cell-depleted mice showed that these mice had higher brain and lung fungal burdens and less alveolar macrophage phagocytosis of C. neoformans than did control and B-1a B cell-reconstituted mice. Taken together, these results establish a mechanistic role for B-1 B cells in the innate B cell response to pulmonary infection with C. neoformans and reveal that IgM-producing B-1a cells, which express germline V(H) genes, bind C. neoformans and contribute to early fungal clearance. Thus, B-1a B cells provide a first line of defense during pulmonary C. neoformans infection in mice.

  18. Characterization of a Reverse-Phase Perfluorocarbon Emulsion for the Pulmonary Delivery of Tobramycin

    PubMed Central

    Babcock, Charlene Irvin; Fabiilli, Mario L.; Pavlovsky, Leonid; Fowlkes, J. Brian; Younger, John G.; Cook, Keith E.

    2014-01-01

    Abstract Background: Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics. Methods: This study examined emulsion aqueous droplet diameter and number density over 24 hr and emulsion and neat PFC viscosity and surface tension. Additionally, Pseudomonas aeruginosa biofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (Ca=0.4, 4, and 40 mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats. Results: The initial aqueous droplet diameter averaged 1.9±0.2 μm with little change over time. Initial aqueous droplet number density averaged 3.5±1.7×109 droplets/mL with a significant (p<0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22±0.03×10–3 Pa·sec. The surface tensions of PFC and emulsion were 15.0±0.1×10–3 and 14.6±0.6×10–3 N/m, respectively, and the aqueous interfacial tensions were 46.7±0.3×10–3 and 26.9±11.0×10–3 N/m (p<0.01), respectively. Biofilm growth decreased markedly with increasing Ca and, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4 hr post delivery, respectively, and significantly (p<0.05) lower serum concentrations compared with aerosolized delivery. Conclusions: The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in

  19. Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry

    PubMed Central

    Przygodzki, Tomasz; Talar, Marcin; Blazejczyk, Agnieszka; Kalchenko, Vyacheslav; Watala, Cezary

    2016-01-01

    Introduction The paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry. Materials and Methods Mice of C57Bl strain were used in the study. ADP was injected to the vena cava and blood flow was monitored with the use of a laser Doppler flowmeter in the mesentery. Measurements in platelet-depleted mice, mice pretreated with cangrelor, an ADP receptor antagonist, and eptifibatide, a blocker of fibrinogen binding to GPIIbIIIa, were conducted as the proof-of-concept in the performed experiments. Intravital microscopy and ex vivo imaging of organs was performed to identify the sites of aggregate formation resulting from ADP injection. Results The injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung. Conclusions Injection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates. PMID:26751810

  20. The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

    PubMed Central

    Zeldin, D C; Plitman, J D; Kobayashi, J; Miller, R F; Snapper, J R; Falck, J R; Szarek, J L; Philpot, R M; Capdevila, J H

    1995-01-01

    Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung. Images PMID:7738183

  1. In-Situ Characterization of Tissue Blood Flow, Blood Content, and Water State Using New Techniques in Magnetic Resonance Imaging.

    NASA Astrophysics Data System (ADS)

    Conturo, Thomas Edward

    Tissue blood flow, blood content, and water state have been characterized in-situ with new nuclear magnetic resonance imaging techniques. The sensitivities of standard techniques to the physiologic tissue parameters spin density (N_{rm r}) and relaxation times (T_1 and T_2 ) are mathematically defined. A new driven inversion method is developed so that tissue T_1 and T_2 changes produce cooperative intensity changes, yielding high contrast, high signal to noise, and sensitivity to a wider range of tissue parameters. The actual tissue parameters were imaged by automated collection of multiple-echo data having multiple T _1 dependence. Data are simultaneously fit by three-parameters to a closed-form expression, producing lower inter-parameter correlation and parameter noise than in separate T_1 or T_2 methods or pre-averaged methods. Accurate parameters are obtained at different field strengths. Parametric images of pathology demonstrate high sensitivity to tissue heterogeneity, and water content is determined in many tissues. Erythrocytes were paramagnetically labeled to study blood content and relaxation mechanisms. Liver and spleen relaxation were enhanced following 10% exchange of animal blood volumes. Rapid water exchange between intracellular and extracellular compartments was validated. Erythrocytes occupied 12.5% of renal cortex volume, and blood content was uniform in the liver, spleen and kidney. The magnitude and direction of flow velocity was then imaged. To eliminate directional artifacts, a bipolar gradient technique sensitized to flow in different directions was developed. Phase angle was reconstructed instead of intensity since the former has a 2pi -fold higher dynamic range. Images of flow through curves demonstrated secondary flow with a centrifugally-biased laminar profile and stationary velocity peaks along the curvature. Portal vein flow velocities were diminished or reversed in cirrhosis. Image artifacts have been characterized and removed. The

  2. The Numerical Predominance and Large Transcriptome Differences of Neutrophils in Peripheral Blood Together Inevitably Account for a Reported Pulmonary Tuberculosis Signature

    PubMed Central

    Deng, Wang-Long; Zhang, Hao

    2017-01-01

    Previous transcriptomic analysis revealed a 393-transcript signature (PTBsig), which is dominated by interferon inducible genes, in whole blood of pulmonary tuberculosis (PTB) patients. Comparisons with a limited set of interferon-driven genes among separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils indicated that the signature is due to changes in neutrophils, the overwhelmingly predominant cell type. By extending the analysis to the entire 393 transcripts of PTBsig and by switching the cell proportions between separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils, we create putative PTBsig for whole blood (pPTBsig) in which CD4+ or CD8+ T cells or monocytes predominated or in which the cell proportions were unchanged. These putative signatures are then compared to the actual reported PTBsig. We show that, because of their predominance in peripheral blood and their larger transcriptional responses, neutrophils were indeed almost exclusively responsible for PTBsig. We caution that the functional significance of changes in other cell types might escape notice in transcriptome analysis that is based upon whole blood. PMID:28265564

  3. Isolation and Characterization of Nontuberculous Mycobacteria from Patients with Pulmonary Tuberculosis in Ghana

    PubMed Central

    Otchere, ID; Asante-Poku, A; Osei-Wusu, S; Aboagye, SY; Yeboah-Manu, D

    2017-01-01

    Background Nontuberculous mycobacterial (NTM) species are assuming public health importance in pulmonary diseases; they are increasingly being isolated, and importantly, most NTMs do not respond to routine tuberculosis (TB) drugs. This study aimed to identify NTMs isolated from pulmonary TB cases and also determine their susceptibility to streptomycin (STR), isoniazid (INH), and rifampicin (RIF). Methods A total of 1755 mycobacterial isolates, obtained between August 2012 and July 2014, from 2036 smear-positive pulmonary cases were identified using polymerase chain reaction amplification of IS6110, and hsp65 gene sequencing analysis. Drug susceptibility testing (DST) was then performed for the identified NTMs against STR, INH, and RIF using microplate Alamar blue assay. The results were analyzed against patients’ biodata for statistical associations. Results Of the 1755 analyzed isolates, we identified 43 (2.5%) NTMs, which included 18 (41.9%) Mycobacterium intracellulare, 13 (30.2%) Mycobacterium avium subs. paratuberculosis, 5 (11.3%) Mycobacterium abscessus, 3 (7.0%) each of Mycobacterium mucogenicum and Mycobacterium colombiense, and 1 (2.3%) Mycobacterium simiae. Patients infected with NTMs (52.0%) were more likely to be human immunodeficiency virus-positive (P = 0.001, odds ratio = 6.6, 95% confidence interval = 2.7–16.2) than those infected with M. tuberculosis complex (5.8%). All the 43 (100%) NTMs were resistant to INH, whereas 32 (74%) and 19 (44%) were resistant to RIF and STR, respectively. Furthermore, 16 (37.2%) NTMs were resistant to all three drugs, 20 were resistant to INH and RIF, and 3 were resistant to STR and INH. All the M. abscessus isolates were resistant to all the three drugs, whereas all the M. avium isolates were resistant to INH and RIF, but only three were resistant to STR. Among the M. intracellulare isolates, 8, 18, and 15 isolates were resistant to STR, INH, and RIF, respectively. Conclusion The observed high-resistance level to

  4. Miliary pulmonary cryptococcosis.

    PubMed

    Kelly, Shane; Marriott, Deborah

    2014-10-01

    A 32-year-old HIV positive male presents with fevers and a non-productive cough. Initial X-ray and subsequent computerised tomography of the chest shows a bilateral miliary pattern of pulmonary infiltration highly suggestive of disseminated tuberculosis. However subsequent results were consistent with disseminated cryptococcosis, including pulmonary involvement, with cryptococcus identified on transbronchial tissue biopsy, and on blood and cerebrospinal fluid cultures. Imaging features of pulmonary cryptococcosis are generally of well-defined pleural-based nodules and less commonly alveolar infiltrates, lymphadenopathy, pleural effusions or cavitating lesions. Miliary pulmonary infiltrates are an exceptionally rare presentation.

  5. Characterization of the normal pulmonary surface and pneumonectomy space by reflected ultrasound

    PubMed Central

    Sperandeo, M.; Varriale, A.; Sperandeo, G.; Bianco, M.R.; Piattelli, M.L.; Bizzarri, M.; Ghittoni, G.; Copetti, M.; Vendemiale, G.

    2011-01-01

    Interest has been increasing in the use of transthoracic ultrasound for the study of the pleuropulmonary disease. US imaging depends mainly on the physical interactions between ultrasound waves and the tissues being examined. In the thoracic region, the prescence of the chest wall and the air-containing pulmonary tissues cause various artifacts that strongly influence the resulting images. At the interface between tissues and air, the ultrasound beam is totally reflected and produces simple reverberation, comet-tail artifacts, and ring-down artifacts. We report the findings of transthoracic ultrasound in normal healthy subjects and in those who had undergone pneumonectomy.This experience shows that, in terms of the ultrasound artifacts mentioned above, the postpneumonectomy cavity is not significantly different from the healthy lung. PMID:23396639

  6. Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure

    NASA Technical Reports Server (NTRS)

    Johnston, C. J.; Finkelstein, J. N.; Gelein, R.; Baggs, R.; Oberdorster, G.; Clarkson, T. W. (Principal Investigator)

    1996-01-01

    Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (approximately 18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460 degrees C for 15 min at an exposure concentration of 5 x 10(5) particles/cm3, equivalent to approximately 50 micrograms/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60-85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-alpha (TNF alpha) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls. In situ sections were hybridized with 33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNF alpha. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNF alpha. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.

  7. Characterization of IL-22 and antimicrobial peptide production in mice protected against pulmonary Cryptococcus neoformans infection.

    PubMed

    Wozniak, Karen L; Hole, Camaron R; Yano, Junko; Fidel, Paul L; Wormley, Floyd L

    2014-07-01

    Cryptococcus neoformans is a significant cause of fungal meningitis in patients with impaired T cell-mediated immunity (CMI). Experimental pulmonary infection with a C. neoformans strain engineered to produce IFN-γ, H99γ, results in the induction of Th1-type CMI, resolution of the acute infection, and protection against challenge with WT Cryptococcus. Given that individuals with suppressed CMI are highly susceptible to pulmonary C. neoformans infection, we sought to determine whether antimicrobial peptides were produced in mice inoculated with H99γ. Thus, we measured levels of antimicrobial peptides lipocalin-2, S100A8, S100A9, calprotectin (S100A8/A9 heterodimer), serum amyloid A-3 (SAA3), and their putative receptors Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE) in mice during primary and recall responses against C. neoformans infection. Results showed increased levels of IL-17A and IL-22, cytokines known to modulate antimicrobial peptide production. We also observed increased levels of lipocalin-2, S100A8, S100A9 and SAA3 as well as TLR4(+) and RAGE(+) macrophages and dendritic cells in mice inoculated with H99γ compared with WT H99. Similar results were observed in the lungs of H99γ-immunized, compared with heat-killed C. neoformans-immunized, mice following challenge with WT yeast. However, IL-22-deficient mice inoculated with H99γ demonstrated antimicrobial peptide production and no change in survival rates compared with WT mice. These studies demonstrate that protection against cryptococcosis is associated with increased production of antimicrobial peptides in the lungs of protected mice that are not solely in response to IL-17A and IL-22 production and may be coincidental rather than functional.

  8. Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure

    NASA Technical Reports Server (NTRS)

    Johnston, C. J.; Finkelstein, J. N.; Gelein, R.; Baggs, R.; Oberdorster, G.; Clarkson, T. W. (Principal Investigator)

    1996-01-01

    Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (approximately 18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460 degrees C for 15 min at an exposure concentration of 5 x 10(5) particles/cm3, equivalent to approximately 50 micrograms/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60-85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-alpha (TNF alpha) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls. In situ sections were hybridized with 33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNF alpha. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNF alpha. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.

  9. Characterization of oxidative stress in blood from diabetic vs. hypercholesterolaemic patients, using a novel synthesized marker.

    PubMed

    Szuchman, Andrea; Aviram, Michael; Musa, Ramadan; Khatib, Soliman; Vaya, Jacob

    2008-02-01

    In the present study, we extend our novel concept of designing and using exogenous markers for the characterization of oxidative stress (OS) and OS-associated diseases. The aim was to use such a synthetic compound as a tool for studying OS in blood from diabetic and hypercholesterolaemic (Hc) patients. The marker used N-linoleoyl tyrosine (LT) was constructed from tyrosine and linoleic acid (LA); both components are known to be easily oxidized upon exposure to different types of reactive oxygen/nitrogen species (ROS/RNS), and to generate specific oxidized products, depending on the type of oxidants present in vivo. Using the LT probe, we showed that the ratios of oxidized LT to total LT (Ox-LT/LT) is significantly higher in blood samples obtained from diabetic patients, than in Hc patients or healthy control subjects. LC/MS analysis revealed that blood from diabetic patients oxidizes the marker with predominant formation of Ox-LT hydroperoxide (LT-OOH) and epoxide (epoxy-LT), where the LA moiety is oxidized to hydroperoxide and to epoxide, respectively. Analysis of oxysterol levels in these samples (GC/MS) revealed that the blood of both diabetic and Hc patients contained significantly more oxysterols than blood of control subjects. Consumption of pomegranate juice by diabetic patients for 3 months suppressed their blood capacity to oxidize the LT and similarly also reduced their blood oxysterol/total cholesterol ratio by 93%. The use of an exogenous marker to characterize OS in blood samples yields important information on the extent of OS, and can provide a fingerprint for the early identification of different pathological conditions associated with OS.

  10. Thromboembolism in pulmonary artery sarcoma.

    PubMed

    Farsad, Mohsen; Pernter, Patrizia; Triani, Antonio; Osele, Luzian; Wiedermann, Christian J

    2009-04-01

    Pulmonary artery sarcoma, although rare, must be considered in the differential diagnosis of pulmonary thromboembolism. Clinically and radiologically, it may imitate pulmonary embolism, making diagnosis difficult and delaying treatment. Patients often have no symptom resolution despite therapeutic anticoagulation. Visualization of filling defects within a pulmonary artery on contrast-enhanced CT cannot reliably differentiate between pulmonary thromboembolism and malignant lesions like leiomyosarcoma. FDG PET-CT offers the potential for identification of malignant lesions. The authors report a case with pulmonary artery thromboembolism due to thrombi formed on a pulmonary artery leiomyosarcoma. Integrated FDG PET-CT showed no FDG-uptake along the major part of the filling defect within the right main pulmonary artery suggesting blood clot and increased uptake along the posterior wall of the right main pulmonary artery and the left lower lobar artery suggesting malignancy.

  11. Changes in ventilatory capacity, exercise capacity, and pulmonary blood flow after lobectomy in patients with lung cancer--which lobectomy has the most loss in exercise capacity?

    PubMed

    Kushibe, Keiji; Kawaguchi, Takeshi; Kimura, Michitaka; Takahama, Makoto; Tojo, Takashi; Taniguchi, Shigeki

    2008-12-01

    The aim of this study was to compare the changes in ventilatory capacity, exercise capacity, and pulmonary blood flow (PBF) in the operated lung after lobectomy according to the lobe resected. Thirty-one patients underwent right upper lobectomy (RUL), 26 left upper lobectomy (LUL), 24 right lower lobectomy (RLL), and 25 left lower lobectomy (LLL). Pulmonary function tests, exercise capacity tests, and perfusion lung scans were performed preoperatively and six months to one year after lobectomy. RUL was associated with significantly less loss in forced vital capacity (FVC) than RLL or LLL (P<0.05). LUL was associated with the greatest loss in maximum oxygen consumption (VO2) (P<0.05). LUL was associated with significantly greater loss in PBF in the operated lung than RUL (P<0.05). LUL had a significantly higher negative value in percentage change in (VO2) --percentage change in FVC, and percentage change in PBF--percentage change in FVC than RLL or LLL (P<0.05). LUL was not associated with the greatest loss in ventilatory capacity or PBF, although it was associated with the greatest loss in . Each lobectomy has its own peculiarity in magnitude of loss in (VO2), PBF or FVC.

  12. Characterization and differentiation of body fluids, putrefaction fluid, and blood using Hounsfield unit in postmortem CT.

    PubMed

    Zech, Wolf-Dieter; Jackowski, Christian; Buetikofer, Yanik; Kara, Levent

    2014-09-01

    The purpose of the present study was to evaluate the ranges of Hounsfield unit (HU) found in body fluids, putrefaction fluids, and blood on postmortem CT and how these ranges are affected by postmortem interval, temperatures, and CT beam energy. Body fluids, putrefaction fluids, and blood from a total of 53 corpses were analyzed to determine the ranges of HU values from postmortem CT images that were taken prior to autopsy. The fluids measured in CT images were obtained at autopsy and examined in terms of macroscopic and microscopic appearances. Body fluids and blood were also collected in plastic bottles, which were subjected to CT scans at different beam energies (80-130 kV) and at various fluid temperatures (4 to 40 °C). At a postmortem interval of 1 to 4 days, the ranges of HU values of the serous fluids (13-38 HU) and the nonsedimented blood (40-88 HU) did not overlap. In the sedimented blood, the upper serum layer exhibited HU value ranges that overlapped with those of the serous fluids. The putrefaction fluids exhibited a range of HU values between 80 and -130 HU. Elevated HU values were observed in fluids with accretive cell impurities. HU values decreased slightly with increasing temperature and CT beam energy. We concluded that serous fluids and blood in fresh corpses can be characterized and differentiated from each other based on HU value ranges. In contrast, body fluids in decomposed corpses cannot be differentiated by their HU value ranges. Different beam energies and corpse temperatures had only minor influences on HU value ranges and therefore should not be obstacles to the differentiation and characterization of body fluids and blood.

  13. Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood.

    PubMed

    Kang, Jun-Gu; Park, Sang-Bum; Seo, Min-Soo; Kim, Hyung-Sik; Chae, Joon-Seok; Kang, Kyung-Sun

    2013-01-01

    Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeutic effect. After eUCB-MSCs transplantation, the core lesion in the SDFT was found to decrease. These results suggest that transplantation using eUCB-MSCs could be another source of cell treatment.

  14. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients.

    PubMed

    Li, Yunsong; Cheng, Xu; Chen, Zhong; Liu, Yi; Liu, Zhidong; Xu, Shaofa

    2017-07-10

    We tested the hypothesis that circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in resected non-small cell lung cancer (NSCLC) patients. CTCs were separated from blood using magnetic beads coated with antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic-activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The association between CTCs and prognosis in these patients was evaluated after a 5-year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that the CTC count in PPB or IPVB was an independent risk factor for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of patients had a shorter median TFS (22 months vs. >60.0 months, p < 0.0012) and shorter OS (27 months vs. >60 months, p < 0.0015). The number of CTCs counted in PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC patients.

  15. [The number of peripheral blood CD11c+ antigen presenting cells increases and their function strengthens in the patients with active pulmonary tuberculosis].

    PubMed

    Lu, Yuanbin; Wang, Wandang; Liu, Ganbin; Zhang, Junai; Gao, Yuchi; Jia, Yan; Yi, Lailong; Xu, Junfa

    2016-03-01

    To detect the percentage of CD11c positive antigen presenting cells (CD11c(+) APCs) in peripheral blood from patients with active pulmonary tuberculosis (APT) and the levels of HLA-DR and CD86. Methods Fifty-two APT patients were enrolled in the study and 15 healthy volunteers served as controls. The frequencies of CD11c(+) APCs and the expressions of HLA-DR and CD86 in CD11c(+) APCs in the peripheral blood were determined by flow cytometry. The percentage of CD11c(+) APCs in the peripheral blood in the patients with APT was much higher than that in the controls. Interestingly, CD11c(+) APCs frequency in post-treatment patients was even higher compared with that in the pre-treatment patients. Furthermore, both HLA-DR(+) CD11c(+) APC frequency and the mean fluorescence intensity (MFI) of HLA-DR in APT patients were higher than those in the controls. Similarly, the percentage of CD86(+) CD11c(+) APCs in the APT patients was also higher than that in the controls. The increase of CD11c(+) APCs with high levels of HLA-DR and CD86 in APT patients suggests that the antigen presenting capacity of APCs is at a high level in APT patients.

  16. Pulmonary delivery of nanosized alendronate for decorporation of inhaled heavy metals: formulation development, characterization and gamma scintigraphic evaluation.

    PubMed

    Sultana, Shaheen; Bhatnagar, Aseem; Rawat, Harish; Nishad, Dhruv Kumar; Talegaonkar, Sushma; Ahmad, Farhan Jalees; Mittal, Gaurav

    2014-08-01

    Medical management of heavy metal toxicity including radioactive ones is the cause of concern because of their increased use in energy production, healthcare and mining. As inhalation is one of the primary routes for internalization, a formulation is needed to trap metal(s) at the portal of entry itself. Objective was to formulate and characterize a nanonized dry powder inhaler (DPI) formulation of alendronate sodium as potential inhalable antidote for chelating metal toxicants. In vitro binding studies of alendronate with respect to seven non-radioactive heavy metals were carried out using UV-spectroscopy and HPLC. Nanonizing of alendronate particles was achieved by antisolvent precipitation using Pluronic-F68 as stabilizer. Characterization was done with the help of SEM, TEM FT-IR, XRD, DSC, NMR spectroscopy and PSD studies. In vitro and in vivo pulmonary deposition studies were carried out using gamma scintigraphy, followed by a limited pharmacokinetic study in humans. In vitro binding studies confirmed the chelating action of alendronate. Anderson cascade impaction showed that nano-alendronate exhibited significantly higher respirable fraction (58.25 ± 1.32%) compared to the micronized form (28.7 ± 0.59%). Scintigraphy results showed significant increase in the alveolar deposition of drug post-nanonizing. Results strongly indicate the role of nano-alendronate DPI as potential inhalable antidote for neutralizing heavy metal toxicity, including radio-metal contamination.

  17. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery.

    PubMed

    Pilcer, Gabrielle; Vanderbist, Francis; Amighi, Karim

    2009-01-05

    Using high-pressure homogenization and spray-drying techniques, novel formulations were developed for manufacturing dry powder for inhalation, composed of a mixture of micro- and nanoparticles in order to enhance lung deposition. Particle size analysis was performed by laser diffraction. Spray-drying was applied in order to retrieve nanoparticles in dried-powder state from tobramycin nanosuspensions. The aerolization properties of the different formulations were evaluated by a multi-stage liquid impinger. Suspensions of nanoparticles of tobramycin containing Na glycocholate at 2% (w/w) relative to tobramycin content and presenting a mean particle size about 200 nm were produced. The results from the spray-dried powders showed that the presence of nanoparticles in the formulations improved particle dispersion properties during inhalation. The fine particle fraction (percentage of particles below 5 microm) increased from 36% for the raw micronized tobramycin material to about 61% for the most effective formulation. These new nanoparticle-containing tobramycin DPI formulations, based on the use of very low level of excipient and presenting high lung deposition properties, offer very important perspectives for improving the delivery of drugs to the pulmonary tract.

  18. Acute tropical pulmonary eosinophilia. Characterization of the lower respiratory tract inflammation and its response to therapy.

    PubMed Central

    Pinkston, P; Vijayan, V K; Nutman, T B; Rom, W N; O'Donnell, K M; Cornelius, M J; Kumaraswami, V; Ferrans, V J; Takemura, T; Yenokida, G

    1987-01-01

    Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu, we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflammatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (n = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54 +/- 5%; normal 2 +/- 5%; P less than 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63 +/- 20 X 10(3)/microliter; normal 0.3 +/- 0.1 X 10(3)/microliter; P less than 0.01). Importantly, when individuals (n = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract. Images PMID:3298321

  19. A porous media theory for characterization of membrane blood oxygenation devices

    NASA Astrophysics Data System (ADS)

    Sano, Yoshihiko; Adachi, Jun; Nakayama, Akira

    2013-07-01

    A porous media theory has been proposed to characterize oxygen transport processes associated with membrane blood oxygenation devices. For the first time, a rigorous mathematical procedure based a volume averaging procedure has been presented to derive a complete set of the governing equations for the blood flow field and oxygen concentration field. As a first step towards a complete three-dimensional numerical analysis, one-dimensional steady case is considered to model typical membrane blood oxygenator scenarios, and to validate the derived equations. The relative magnitudes of oxygen transport terms are made clear, introducing a dimensionless parameter which measures the distance the oxygen gas travels to dissolve in the blood as compared with the blood dispersion length. This dimensionless number is found so large that the oxygen diffusion term can be neglected in most cases. A simple linear relationship between the blood flow rate and total oxygen transfer rate is found for oxygenators with sufficiently large membrane surface areas. Comparison of the one-dimensional analytic results and available experimental data reveals the soundness of the present analysis.

  20. Pulmonary vein imaging: comparison of 3D magnetic resonance angiography with 2D cine MRI for characterizing anatomy and size.

    PubMed

    Syed, Mushabbar A; Peters, Dana C; Rashid, Haroon; Arai, Andrew E

    2005-01-01

    Pulmonary vein imaging is integral for planning atrial fibrillation ablation procedures. We tested the feasibility of quantifying pulmonary vein ostial diameter using two-dimensional cine cardiac magnetic resonance (2D cine CMR) and three-dimensional magnetic resonance angiography (3D MRA). Nine patients with a history of atrial fibrillation and 20 normal volunteers underwent 2D cine CMR and contrast-enhanced 3D MRA of pulmonary veins on a 1.5 T scanner. Pulmonary vein ostial diameters were measured and pulmonary vein vessel border sharpness was graded qualitatively. Both techniques provided excellent pulmonary vein imaging; however, 3D MRA was faster to perform. The average difference between the systolic and diastolic pulmonary vein diameter was 2.5 mm (23.2%, p < 0.0001) in normal volunteers and 2.2 mm (16.9%, p < 0.0001) in atrial fibrillation patients. The ostial diameter measurements by 3D MRA were significantly larger than on 2D cine CMR. Additionally, the pulmonary vein borders appeared sharper with 2D cine CMR compared to 3D MRA. In conclusion, the 2D images can resolve differences in diameter across the cardiac cycle, while the 3D images provide high quality anatomical depiction but blur borders due to pulsatile motion. We suggest a protocol combining 2D cine CMR and 3D MRA for comprehensive evaluation of pulmonary veins.

  1. Label-free characterization of white blood cells by measuring 3D refractive index maps

    PubMed Central

    Yoon, Jonghee; Kim, Kyoohyun; Park, HyunJoo; Choi, Chulhee; Jang, Seongsoo; Park, YongKeun

    2015-01-01

    The characterization of white blood cells (WBCs) is crucial for blood analyses and disease diagnoses. However, current standard techniques rely on cell labeling, a process which imposes significant limitations. Here we present three-dimensional (3D) optical measurements and the label-free characterization of mouse WBCs using optical diffraction tomography. 3D refractive index (RI) tomograms of individual WBCs are constructed from multiple two-dimensional quantitative phase images of samples illuminated at various angles of incidence. Measurements of the 3D RI tomogram of WBCs enable the separation of heterogeneous populations of WBCs using quantitative morphological and biochemical information. Time-lapse tomographic measurements also provide the 3D trajectory of micrometer-sized beads ingested by WBCs. These results demonstrate that optical diffraction tomography can be a useful and versatile tool for the study of WBCs. PMID:26504637

  2. Label-free characterization of white blood cells by measuring 3D refractive index maps.

    PubMed

    Yoon, Jonghee; Kim, Kyoohyun; Park, HyunJoo; Choi, Chulhee; Jang, Seongsoo; Park, YongKeun

    2015-10-01

    The characterization of white blood cells (WBCs) is crucial for blood analyses and disease diagnoses. However, current standard techniques rely on cell labeling, a process which imposes significant limitations. Here we present three-dimensional (3D) optical measurements and the label-free characterization of mouse WBCs using optical diffraction tomography. 3D refractive index (RI) tomograms of individual WBCs are constructed from multiple two-dimensional quantitative phase images of samples illuminated at various angles of incidence. Measurements of the 3D RI tomogram of WBCs enable the separation of heterogeneous populations of WBCs using quantitative morphological and biochemical information. Time-lapse tomographic measurements also provide the 3D trajectory of micrometer-sized beads ingested by WBCs. These results demonstrate that optical diffraction tomography can be a useful and versatile tool for the study of WBCs.

  3. Characterizing human skin blood flow regulation in response to different local skin temperature perturbations.

    PubMed

    Wu, Y; Nieuwenhoff, M D; Huygen, F J P M; van der Helm, F C T; Niehof, S; Schouten, A C

    2017-05-01

    Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Blood

    MedlinePlus

    ... spans vary from a few days to months. New cells are constantly being formed in the bone marrow. ... the bloodstream and are constantly being replaced by new cells. Blood also contains important proteins called clotting factors , ...

  5. Feasibility of Doppler variance imaging for red blood cell aggregation characterization

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Ahn, Yeh-Chan; Chen, Zhongping

    2009-11-01

    An abnormal level of red blood cell (RBC) aggregation is a clinical condition associated with many pathologies. Our purpose is to investigate the feasibility of spectral domain phase-resolved optical Doppler tomography incorporated with Doppler variance imaging to characterize RBC aggregation in flowing blood. Variance/standard deviation (SD) of the Doppler frequency spectrum of porcine blood flowing through a glass tube (diameter 300 μm) at 4.7 mm/s is measured. For nonaggregating RBCs with hematocrits of 20, 40, and 60%, the mean centerline SD values were 34.2+/-1.2, 47.8+/-1.0, and 47.2+/-0.5, respectively. After dextran 500 induction, the SD value decreased significantly to 29.9+/-0.7, 37.9+/-3.0, and 40.1+/-0.6 (P<0.01) in the aggregated blood, respectively. The results demonstrate that Doppler variance imaging using the SD value is capable of differentiating normal and aggregated blood.

  6. Characterization of retinal blood vessel by laser speckle correlation time constant (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Lin, Meng-Chieh; Lai, Wan-Huseh; Tien, Chung-Hao

    2016-09-01

    Laser speckle imaging is an optical metrology technique for examining various forms of object motion in fields from material engineering to bio-medical. As highly coherent illumination encounters the rough surface or scattering medium, due to the multiple interference, the randomly distributed black and white spots formed and are known as speckles. By analyzing speckle images, surface information or scattering medium motion could be recovered. In this study, an optical system for acquiring speckle images from rabbit retina is built for characterizing the blood vessel properties with speckle correlation time constant. As laser illuminates onto the rabbit retina, speckles are formed due to the moving red blood cells inside the retinal blood vessel. The intensity of speckles fluctuate along time and are recorded with high speed CMOS at frame rate 150 frames per second. Speckle correlation time constant describe the relation between frames as the decay rate. Two approaches are used for the processing of image sequences for correlation time constant, one is utilizing asymptotic equation from speckle contrast result, and another is correlation based approach. To determine the performance of our system and algorithms, we compare two regions on the retina with different properties, one region contains faster blood flow while another with slower blood flow. Both approaches shows distinct differences in the value of correlation time constant of two regions.

  7. Tracheal instillation of diesel exhaust particles component causes blood and pulmonary neutrophilia and enhances myocardial oxidative stress in mice.

    PubMed

    Yokota, Syunji; Seki, Takayuki; Naito, Yukiko; Tachibana, Shigehiro; Hirabayashi, Naoyuki; Nakasaka, Toshiaki; Ohara, Naoki; Kobayashi, Hiroyuki

    2008-12-01

    The influences of inhaling particulate air-pollutants on hematopoiesis and myocardial oxidative stress were investigated in mice by intratracheal instillation (IT) of diesel exhaust particles (DEP), its dichloromethane soluble-component (DMSC) or residual particle-component (RPC). After IT, time courses of cytokine levels in bronchial alveolar lavage fluid (BALF), peripheral blood cell count, myocardial myeloperoxidase (MPO) activity and myocardial chemokine levels were observed for 24 hr. RPC caused sustained blood neutrophilia while that caused by DEP and DMSC was transient. RPC also caused sustained elevations of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6 levels in BALF. Furthermore, IL-1beta level in BALF in the RPC group was significantly elevated at 24 hr after IT. Significant positive correlations were observed between blood neutrophil count and IL-6/G-CSF levels in BALF. MPO activity in the myocardium was increased by RPC at 12 and 24 hr after IT while the activities in the kidney and the liver were not affected. Significant correlation was also observed between myocardial MPO activity and blood neutrophil count at 12 hr after IT, for all three substances. From these results, it was concluded that particle component of DEP may enhance myocardial oxidative stress via blood neutrophilia and the elevation of cytokine levels in BALF.

  8. Evaluation of high-concentration sevoflurane for induction and nasotracheal intubation without muscle relaxant for infants with different pulmonary blood flow undergoing surgery for congenital heart diseases.

    PubMed

    Wang, Kai-Yuan; Wang, Hong-Wu; Xin, Lian-Feng; Wang, Yong-Wang; Xue, Yu-Liang

    2011-12-01

    Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases. Fifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded. Times to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively. Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF

  9. The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol.

    PubMed

    Inan, Umit Ubeyt; Ermis, Sitki Samet; Orman, Ayse; Onrat, Ersel; Yucel, Aylin; Ozturk, Faruk; Asagidag, Ali; Celik, Atac

    2004-08-01

    This study evaluated systemic and ocular acute safety and intraocular pressure (IOP)-lowering efficacy of travoprost 0.004% and bimatoprost 0.03%, compared to brimonidine 0.2% and betaxolol 0.25% in healthy subjects. Nineteen (19) young men, ages between 24 and 42, were enrolled in a single-center, institutional randomized, double-masked, crossover clinical trial. Baseline IOP, heart rate, blood pressure, and respiratory rate were recorded at hour 0. At minute 30, heart rate, blood pressure, respiratory rate, and spirometry were measured. At hour 1, color Doppler imaging of retrobulbar vessels was performed. At hour 2, heart rate, blood pressure, and respiratory rate were measured; spirometry and a 15-minute treadmill test were performed. The same protocol was applied after one drop of a study medication was instilled into each eye on four subsequent visits at 5-day intervals. Travoprost and bimatoprost did not cause significant reductions in systolic blood pressure during exercise and recovery. The mean respiratory rate and forced expiratory volume in 1 second were not significantly altered by any study medication. Travoprost reduced the resistive index and increased blood velocities in the ophthalmic artery and its branches. Bimatoprost caused a significant increase in end diastolic velocity of the ophthalmic artery. At hour 6, all medications reduced IOP significantly (p < 0.05). The most frequent ocular side effect of travoprost and bimatoprost was conjunctival hyperemia. Travoprost and bimatoprost were found to be systemically safe and caused an increase in blood-flow velocities of the retrobulbar vessels after a single-dose application. Their ocular hypotensive effect was comparable to that of brimonidine and greater than that of betaxolol in healthy subjects.

  10. Pulmonary angiography

    MedlinePlus

    ... Pulmonary arteriography; Pulmonary angiogram; Angiogram of the lungs Images Pulmonary arteries References Jackson JE, Meaney JFM. Angiography. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  11. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  12. Pulmonary arterial hypertension in congenital heart diseases.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2009-08-01

    Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.

  13. [Effect of changes in airway pressure and the inspiratory volume on the fluid filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused with blood and acellular solution].

    PubMed

    Crespo, Astrid; Novoa, Eva; Urich, Daniela; Trejo, Humberto; Pezzulo, Alejandro; Sznajder, Jacob I; Livia, Fernández; Sánchez-de León, Roberto

    2006-12-01

    It has been reported that ventilation with large tidal volumes causes pulmonary edema in rats by the stimulation and release of proinflammatory mediators. Our objective was to determine the level at which volutrauma induced by changes in Airway Pressure (PAW) and Inspiratory Volume (VI) produce significant changes on the Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP) in lungs perfused with blood (cellular groups) or with a buffer-albumin solution (acellular groups), with a Positive End Expiratory Pressure (PEEP) 0 or 2 cmH2O and to study the effect of a vasodilator with antiinflammatory properties (fenoterol) in blood-perfused groups. Three experimental groups were used: the cellular groups studied the effect of increased PAW and IV in isolated lungs perfused with blood and PEEP 0 and 2; the acellular groups studied the increased PAW and IV in isolated lungs perfused with a buffer-albumin solution and PEEP 0 and 2; The fenoterol group studied the effect of increased PAW and IV in isolated lungs perfused with blood + fenoterol and PEEP 2. The results show that an increase of FFR is produced earlier in acellular groups than in cellular ones and that the damage in cellular groups is microscopically and macroscopically inferior when compared to acellular groups. Fenoterol did not inhibit edema formation, and that PEEP 2, both in the cellular and the acellular groups, has a protective effect. We propose the possible existence of mediators with protective effects against the formation of pulmonary edema in the blood. These data suggest that volutrauma induced pulmonary edema has a predominantly traumatic origin when the lungs are perfused with blood.

  14. Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease.

    PubMed

    Kato, Ryo; Mizuno, Shiro; Kadowaki, Maiko; Shiozaki, Kohei; Akai, Masaya; Nakagawa, Ken; Oikawa, Taku; Iguchi, Masaharu; Osanai, Kazuhiro; Ishizaki, Takeshi; Voelkel, Norbert F; Toga, Hirohisa

    2016-10-27

    Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34(+) progenitor cells to examine whether these genes are associated with COPD development. This study included 358 patients with a smoking history of more than 10 pack-years. RNA was extracted from blood samples and from CD34(+) progenitor cells treated with cigarette smoke extract (CSE), followed by assessment of CD31, CD34, Sirt1 mRNA, miR-34a, and miR-126-3p expression by real-time RT-PCR. The expression of CD31, CD34, Sirt1 mRNAs, and miR-126-3p decreased and that of miR-34a increased in moderate COPD compared with that in control smokers. However, no significant differences in these genes were observed in blood cells from patients with severe COPD compared with those in control smokers. CSE significantly decreased Sirt1 and increased miR-34a expression in cultured progenitor cells. Sirt1 expression in blood cells from patients with COPD could be a biomarker for disease stability in patients with moderate COPD. MiR-34a may participate in apoptosis and/or senescence of EPCs in smokers. Decreased expression of CD31, CD34, and miR-126-3p potentially represents decreased numbers of EPCs in blood cell from patients with COPD.

  15. Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing.

    PubMed

    Logue, Kyle; Keven, John Bosco; Cannon, Matthew V; Reimer, Lisa; Siba, Peter; Walker, Edward D; Zimmerman, Peter A; Serre, David

    2016-03-01

    Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources.

  16. Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing

    PubMed Central

    Logue, Kyle; Keven, John Bosco; Cannon, Matthew V.; Reimer, Lisa; Siba, Peter; Walker, Edward D.; Zimmerman, Peter A.; Serre, David

    2016-01-01

    Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources. PMID:26963245

  17. Development and characterization of a blood mimicking fluid for high intensity focused ultrasound.

    PubMed

    Liu, Yunbo; Maruvada, Subha; King, Randy L; Herman, Bruce A; Wear, Keith A

    2008-09-01

    A blood mimicking fluid (BMF) has been developed for the acoustic and thermal characterizations of high intensity focused ultrasound (HIFU) ablation devices. The BMF is based on a degassed and de-ionized water solution dispersed with low density polyethylene microspheres, nylon particles, gellan gum, and glycerol. A broad range of physical parameters, including attenuation coefficient, speed of sound, viscosity, thermal conductivity, and diffusivity, were characterized as a function of temperature (20-70 degrees C). The nonlinear parameter B/A and backscatter coefficient were also measured at room temperature. Importantly, the attenuation coefficient is linearly proportional to the frequency (2-8 MHz) with a slope of about 0.2 dB cm(-1) MHz(-1) in the 20-70 degrees C range as in the case of human blood. Furthermore, sound speed and bloodlike backscattering indicate the usefulness of the BMF for ultrasound flow imaging and ultrasound-guided HIFU applications. Most of the other temperature-dependent physical parameters are also close to the reported values in human blood. These properties make it a unique HIFU research tool for developing standardized exposimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU ablation devices.

  18. Identification of guinea pig gammadelta T cells and characterization during pulmonary tuberculosis.

    PubMed

    Xiong, Xiaowei; Morita, Craig T; Bukowski, Jack F; Brenner, Michael B; Dascher, Christopher C

    2004-11-01

    Guinea pigs are an alternative small animal model for many disease studies. Here we describe a pan-gammadelta monoclonal antibody (anti-TCRdelta1) specific for the constant region of human T cell receptor delta chains that cross-reacts with a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and distribution of this subpopulation is consistent with the guinea pig gammadelta T cell subset. FACS analysis of fresh PBMC and splenocytes from naïve guinea pigs revealed the presence of a subset of cells that stained with the anti-TCRdelta1 mAb. The relative percentage of anti-TCRdelta1 positive cells in PBMC and tissues is similar to that described for gammadelta T cells in other species. Immunohistochemistry of tissues also revealed a distribution of anti-TCRdelta1 positive cells consistent with gammadelta T cells. These data are further supported by staining of a polyclonal guinea pig T cell line that became progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis revealed no apparent changes in the steady-state percentage of blood gammadelta+ T cells. Taken together, these data suggest that the anti-TCRdelta1 antibody recognizes the gammadelta T cell subset in guinea pigs. This reagent may be useful for examining gammadelta T cells in various disease models where the guinea pig is a more desirable model for study.

  19. Inhaled treprostinil and pulmonary arterial hypertension

    PubMed Central

    Nadler, Samuel T; Edelman, Jeffrey D

    2010-01-01

    Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432

  20. Retrograde pulmonary perfusion as an adjunct to standard pulmonary embolectomy for acute pulmonary embolism.

    PubMed

    Spagnolo, Salvatore; Barbato, Luciano; Grasso, Maria Antonia; Tesler, Ugo Filippo

    2014-01-01

    Mortality rates for pulmonary embolectomy in patients with acute massive pulmonary embolism have decreased in recent years. However, it still ranges from 30 to 45% when surgery is performed on critically ill patients, and the mortality rates reach 60% in patients who have experienced a cardiac arrest before the procedure. The causes of death in these patients are generally attributed to right heart failure due to persistent pulmonary hypertension, intractable pulmonary oedema, and massive parenchymal and intrabronchial haemorrhage. Clinical and experimental findings indicate that venous air embolism causes severe or even lethal damage to the pulmonary microvasculature and the lung parenchyma consequent to the release of endothelium-derived cytokines. These findings are similar to those observed when severely compromised patients undergo pulmonary embolectomy for air entrapped in the pulmonary artery during embolectomy, which may lead to fatal outcomes. Retrograde pulmonary perfusion (RPP), besides enabling the removal of residual thrombotic material from the peripheral branches of the pulmonary artery, fills the pulmonary artery with blood and prevents pulmonary air embolism. We believe that the use of RPP as an adjunct to conventional pulmonary embolectomy decreases the morbidity and mortality rates associated with pulmonary embolectomy in critically ill patients.

  1. American Thoracic Society/National Heart, Lung, and Blood Institute Asthma-Chronic Obstructive Pulmonary Disease Overlap Workshop Report.

    PubMed

    Woodruff, Prescott G; van den Berge, Maarten; Boucher, Richard C; Brightling, Christopher; Burchard, Esteban G; Christenson, Stephanie A; Han, MeiLan K; Holtzman, Michael J; Kraft, Monica; Lynch, David A; Martinez, Fernando D; Reddel, Helen K; Sin, Don D; Washko, George R; Wenzel, Sally E; Punturieri, Antonello; Freemer, Michelle M; Wise, Robert A

    2017-08-01

    Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma and COPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions.

  2. Molecular characterization of hepatitis C virus genotype 6 subtypes in Thai blood donors.

    PubMed

    Sistayanarain, Anchalee; Chaiwong, Suriya

    2017-02-01

    Hepatitis C virus (HCV) genotype is important for identifying effective antiviral therapy, evaluating pathogenic severity, and tracking transmission routes. In Thailand, HCV genotypes 3 and 1 are the most common. We have previously demonstrated an increasing appearance of genotype 6 in HCV infections in Thailand. However, only limited epidemiological data on genotype 6 in Thailand are available. This study aimed to characterize HCV genotype 6 among apparently healthy Thai blood donors. In total, 240 blood samples were collected from Phitsanulok Regional Blood Center, Phitsanulok, Thailand. RNA was reverse transcribed and amplified by the nested polymerase chain reaction. HCV genotyping was performed by direct sequencing and phylogenetic tree analysis of core sequences. Amino acid polymorphism of various subtypes of HCV genotype 6 was investigated. Of the 240 samples, 192 were successfully sequenced for the core region and 84 were determined to be of HCV genotype 6 by phylogenetic analysis. The most prevalent HCV-6 subtypes were 6f > 6n > 6c > 6i. Amino acid sequences of the partial core region among these four subtypes differed by one to seven residues. For HCV-6, the subtype 6f was commonly found in Thai blood donors. Comparison of core protein from various HCV-6 subtypes showed substantial polymorphisms, which may form the basis of future studies using samples from patients with clear HCV histories. This feature can be applied to therapies tailored to particular genotype variants. Copyright © 2015. Published by Elsevier B.V.

  3. How should the optical tweezers experiment be used to characterize the red blood cell membrane mechanics?

    PubMed

    Sigüenza, Julien; Mendez, Simon; Nicoud, Franck

    2017-05-03

    Stretching red blood cells using optical tweezers is a way to characterize the mechanical properties of their membrane by measuring the size of the cell in the direction of the stretching (axial diameter) and perpendicularly (transverse diameter). Recently, such data have been used in numerous publications to validate solvers dedicated to the computation of red blood cell dynamics under flow. In the present study, different mechanical models are used to simulate the stretching of red blood cells by optical tweezers. Results first show that the mechanical moduli of the membranes have to be adjusted as a function of the model used. In addition, by assessing the area dilation of the cells, the axial and transverse diameters measured in optical tweezers experiments are found to be insufficient to discriminate between models relevant to red blood cells or not. At last, it is shown that other quantities such as the height or the profile of the cell should be preferred for validation purposes since they are more sensitive to the membrane model.

  4. Influence of crystalloid and colloid fluid infusion and blood withdrawal on pulmonary bioimpedance in an animal model of mechanical ventilation.

    PubMed

    Bodenstein, Marc; Wang, Hemei; Boehme, Stefan; Vogt, Andreas; Kwiecien, Robert; David, Matthias; Markstaller, Klaus

    2012-07-01

    Electrical impedance tomography (EIT) is considered useful for monitoring regional ventilation and aeration in intensive-care patients during mechanical ventilation. Changes in their body fluid state modify the electrical properties of lung tissue and may interfere with the EIT measurements of lung aeration. The aim of our study was to assess the effects of crystalloid and colloid infusion and blood withdrawal on bioimpedance determined by EIT in a chest cross-section. Fourteen anaesthetized mechanically ventilated pigs were subjected to interventions affecting the volume state (crystalloid and colloid infusion, blood withdrawal). Six animals received additional crystalloid fluids (fluid group) whereas eight did not (no-fluid group). Global and regional relative impedance changes (RIC, dimensionless unit) were determined by backprojection at end-expiration. Regional ventilation distribution was analyzed by calculating the tidal RIC in the same regions. Colloid infusion led to a significant fall in the global end-expiratory RIC (mean differences: fluid: -91.2, p < 0.001, no-fluid: -38.9, p < 0.001), which was partially reversed after blood withdrawal (mean differences, fluid: +45.1, p = 0.047 and no-fluid: +26.2, p = 0.009). The RIC was significantly lower in the animals with additional crystalloids (mean group difference: 45.5, p < 0.001). Global and regional tidal volumes were not significantly affected by the fluid and volume states.

  5. Chinese patent medicine for chronic obstructive pulmonary disease based on principles of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm: a systematic review of randomized controlled trials.

    PubMed

    Liu, Wei; Yang, Shuang; Fu, Min; Li, Jian; Song, Yaling; Wei, Baolin; Liu, Enshun; Sun, Zengtao

    2015-02-01

    To assess the efficacy and safety of Chinese patent medicine (CPM) with the principle of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm (TQ-PBC-RP) in the management of stable chronic obstructive pulmonary disease (COPD). A systematic review of randomized controlled trials (RCTs) identified from electronic databases and print was conducted. RCTs testing CPMs with TQ-PBC-RP against any type of controlled intervention in patients with stable COPD and assessing clinically relevant outcomes were included. Methodological quality was evaluated with the risk of bias tool according to systematic review handbook 5.0.2. Quality of evidence was estimated by the rating approach developed by the Grading of Recommendations, Assessment, Development, and Evaluation Working Group. Thirteen eligible RCTs with 12 oral CPMs were tested. Significant differences between groups in favor of CPMs were not reported in all trials. Most trials included were deemed to be of low methodological quality with poor evidence quality. Because of large data heterogeneity, statistical pooling was not performed for all outcomes. The effectiveness of CPM in the treatment of stable COPD is not supported by evidence. Currently, evidence from RCTs is scarce and methodologically weak. Considering the popularity of CPMs among patients undergoing COPD, rigorously designed trials are warranted.

  6. Magnetic characterization of human blood in the atherosclerotic process in coronary arteries

    NASA Astrophysics Data System (ADS)

    Janus, B.; Bućko, M. S.; Chrobak, A.; Wasilewski, J.; Zych, M.

    2011-03-01

    In the last decades there has been an increasing interest in biomagnetism—a field of biophysics concerned with the magnetic properties of living organisms. Biomagnetism focuses on the measurement of magnetic properties of biological samples in the clinical environment. Progress in this field can provide new data for the understanding of the pathomechanism of atherosclerosis and support the diagnostic options for the evaluation and treatment of atherothrombotic complications. Lyophilized human blood samples from patients with atherosclerotic lesions (calcium scoring (CS) CS>0) and without atherosclerotic lesions (CS=0) were magnetically investigated. Magnetic measurements (performed in room and low temperature) indicated significant magnetic differences between these two groups of patients. Atherosclerotic blood samples are characterized by higher concentration of ferrimagnetic particles (magnetite and/or maghemite) and significant changes in the superparamagnetic behaviour. This research presents that magnetometry, in combination with medical research can lead to a better understanding of iron physiology in the atherosclerotic process.

  7. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    SciTech Connect

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%.

  8. Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood

    PubMed Central

    Kang, Jun-Gu; Park, Sang-Bum; Seo, Min-Soo; Kim, Hyung-Sik

    2013-01-01

    Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeutic effect. After eUCB-MSCs transplantation, the core lesion in the SDFT was found to decrease. These results suggest that transplantation using eUCB-MSCs could be another source of cell treatment. PMID:23820166

  9. Application of image flow cytometry for the characterization of red blood cell morphology

    NASA Astrophysics Data System (ADS)

    Pinto, Ruben N.; Sebastian, Joseph A.; Parsons, Michael; Chang, Tim C.; Acker, Jason P.; Kolios, Michael C.

    2017-02-01

    Red blood cells (RBCs) stored in hypothermic environments for the purpose of transfusion have been documented to undergo structural and functional changes over time. One sign of the so-called RBC storage lesion is irreversible damage to the cell membrane. Consequently, RBCs undergo a morphological transformation from regular, deformable biconcave discocytes to rigid spheroechinocytes. The spherically shaped RBCs lack the deformability to efficiently enter microvasculature, thereby reducing the capacity of RBCs to oxygenate tissue. Blood banks currently rely on microscope techniques that include fixing, staining and cell counting in order to morphologically characterize RBC samples; these methods are labor intensive and highly subjective. This study presents a novel, high-throughput RBC morphology characterization technique using image flow cytometry (IFC). An image segmentation template was developed to process 100,000 images acquired from the IFC system and output the relative spheroechinocyte percentage. The technique was applied on samples extracted from two blood bags to monitor the morphological changes of the RBCs during in vitro hypothermic storage. The study found that, for a given sample of RBCs, the IFC method was twice as fast in data acquisition, and analyzed 250-350 times more RBCs than the conventional method. Over the lifespan of the blood bags, the mean spheroechinocyte population increased by 37%. Future work will focus on expanding the template to segregate RBC images into more subpopulations for the validation of the IFC method against conventional techniques; the expanded template will aid in establishing quantitative links between spheroechinocyte increase and other RBC storage lesion characteristics.

  10. Characterization of endothelial colony-forming cells from peripheral blood samples of adult horses.

    PubMed

    Salter, Margaret M; Seeto, Wen J; DeWitt, Blake B; Hashimi, Sarah A; Schwartz, Dean D; Lipke, Elizabeth A; Wooldridge, Anne A

    2015-02-01

    To isolate and characterize endothelial colony-forming cells (ECFCs; a subtype of endothelial progenitor cells) from peripheral blood samples of horses. Jugular venous blood samples from 24 adult horses. Blood samples were cultured in endothelial cell growth medium. Isolated ECFCs were characterized by use of functional assays of fluorescence-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) uptake and vascular tubule formation in vitro. Expression of endothelial (CD34, CD105, vascular endothelial growth factor receptor 2, and von Willebrand factor) and hematopoietic (CD14) cell markers was assessed through indirect immunofluorescence assay and flow cytometry. The number of passages before senescence was determined through serial evaluation of DiI-Ac-LDL uptake, vascular tubule formation, and cell doubling rates. Samples from 3 horses produced colonies at 12 ± 2.5 days with characteristic endothelial single layer cobblestone morphology and substantial outgrowth on expansion. Equine ECFCs formed vascular tubules in vitro and had uptake of DiI-Ac-LDL (74.9 ± 14.7% positive cells). Tubule formation and DiI-Ac-LDL uptake diminished by passage 5. Equine ECFCs tested positive for von Willebrand factor, vascular endothelial growth factor receptor 2, CD34, and CD105 with an immunofluorescence assay and for CD14 and CD105 via flow cytometry. ECFCs can be isolated from peripheral blood of horses and have characteristics similar to those described for other species. These cells may have potential therapeutic use in equine diseases associated with ischemia or delayed vascularization.

  11. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches

    PubMed Central

    2011-01-01

    Background Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. Methods We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. Results The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID). Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response. The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly

  12. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches.

    PubMed

    Renard, Didier; Looby, Michael; Kramer, Benjamin; Lawrence, David; Morris, David; Stanski, Donald R

    2011-04-26

    Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID). Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response

  13. Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids.

    PubMed

    Zhou, Di; Li, Hongshan; Wang, Yaning; Hochhaus, Guenther; Sinha, Vikram; Zhao, Liang

    2015-08-01

    The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development.

  14. Characterization and determination of six flavonoids in the ethnomedicine "Dragon's Blood" by UPLC-PAD-MS.

    PubMed

    Yi, Tao; Tang, Yina; Zhang, Jianye; Zhao, Zhongzhen; Yang, Zhijun; Chen, Hubiao

    2012-10-10

    "Dragon's Blood" (DB) has long been used as an ethnomedicine in China to invigorate blood circulation for the treatment of traumatic injuries, blood stasis and pain. To comprehensively assess the quality of DB medicine, a precise and accurate method that can rapidly separate, characterize and quantify multiple active components of DB is crucial. An ultra performance liquid chromatography (UPLC) coupled with photodiode array detection (PAD) and electrospray ionization mass spectrometry (ESI-MS) method was developed for characterization and determination of six flavonoids in DB. A comprehensive validation of the developed method was conducted, and confirmed that the method presented good sensitivity, precision and accuracy. All linear regressions were acquired with R2 > 0.99, and the limits of detection ranged from 0.06 to 0.83 ng. The relative standard deviation (RSD) values were found to be within the range 1.4-3.8% for the method repeatability test. Recovery studies for the quantified compounds were found to be within the range 94.2-102.8% with RSD less than 4.9%. DB samples collected from different geographical regions were analyzed by the present method, and the results demonstrated that the contents of the six flavonoids in DB samples varied significantly. Three major active components among the six flavonoids, namely dracorhodin, (2S)-5-methoxyflavan-7-ol and (2S)-5-methoxy-6-methylflavan-7-ol, are suggested as the index for DB quality evaluation. Overall, the present hyphenation method is highly efficient and reliable, and hence suitable for the characterization and determination of the flavonoids of DB ethnomedicine.

  15. Whole Blood Interferon-γ Release Assay Is Insufficient for the Diagnosis of Sputum Smear Negative Pulmonary Tuberculosis

    PubMed Central

    Park, HeeJin; Shin, Jung Ar; Kim, Hyung Jung; Ahn, Chul Min

    2014-01-01

    Purpose We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guérin (BCG) vaccination rate. Materials and Methods We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. Results Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. Conclusion Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate. PMID:24719140

  16. Whole blood interferon-γ release assay is insufficient for the diagnosis of sputum smear negative pulmonary tuberculosis.

    PubMed

    Park, HeeJin; Shin, Jung Ar; Kim, Hyung Jung; Ahn, Chul Min; Chang, Yoon Soo

    2014-05-01

    We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.

  17. Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer

    NASA Astrophysics Data System (ADS)

    Muthuvelu, K.; Shanmugam, Sivabalan; Koteeswaran, Dornadula; Srinivasan, S.; Venkatesan, P.; Aruna, Prakasarao; Ganesan, Singaravelu

    2011-03-01

    In this study the diagnostic potential of synchronous luminescence spectroscopy (SLS) technique for the characterization of normal and different pathological condition of cervix viz., moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) and well differentiated squamous cell carcinoma (WDSSC). Synchronous fluorescence spectra were measured for 70 abnormal cases and 30 normal subjects. Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC and WDSCC cervical blood formed elements were obtained. The synchronous luminescence spectra of formed elements of normal and abnormal cervical cancer patients were subjected to statistical analysis. Synchronous luminescence spectroscopy provides 90% sensitivity and 92.6% specificity.

  18. Liposome-encapsulated hemoglobin as an artificial red blood cell: characterization and scale-up.

    PubMed

    Vidal-Naquet, A; Gossage, J L; Sullivan, T P; Haynes, J W; Gilruth, B H; Beissinger, R L; Sehgal, L R; Rosen, A L

    1989-01-01

    Encapsulation methods using high pressure extrusion and homogenization were developed which produce hemoglobin-containing liposomes, approximately one micron or less in diameter with an oxygen-carrying capacity of more than half that of red blood cells (RBCs). These methods were developed for scaling-up liposome-encapsulated hemoglobin (LEH) production. Previously, the lack of adequate scale-up methods has been a serious barrier to full scale efficacy and toxicity testing for all the researchers engaged in such investigations. The scale-up methods and characterization of the resulting LEH preparations are presented.

  19. Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice.

    PubMed

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Geretto, Marta; Micale, Rosanna T; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E; De Flora, Silvio

    2016-12-20

    Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention.

  20. Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

    PubMed Central

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

    2016-01-01

    Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention. PMID:27713172

  1. Pulmonary ultrasound and pulse oximetry versus chest radiography and arterial blood gas analysis for the diagnosis of acute respiratory distress syndrome: a pilot study.

    PubMed

    Bass, Cameron M; Sajed, Dana R; Adedipe, Adeyinka A; West, T Eoin

    2015-07-21

    200), sensitivity was 64% (95% CI 31-89) and specificity was 86% (95% CI 65-97). Excluding repeat assessments and independent interpretation of ultrasound images did not significantly alter the sensitivity measures. Pulse oximetry and pulmonary ultrasound may be useful tools to screen for, or rule out, impaired oxygenation or lung abnormalities consistent with ARDS in under-resourced settings where arterial blood gas testing and chest radiography are not readily available.

  2. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

    PubMed

    Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

    2015-02-01

    Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

  3. Immunohistochemical Characterization of the Chemosensory Pulmonary Neuroepithelial Bodies in the Naked Mole-Rat Reveals a Unique Adaptive Phenotype

    PubMed Central

    Pan, Jie; Park, Thomas J.; Cutz, Ernest; Yeger, Herman

    2014-01-01

    The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR’s adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and

  4. Characterization of the cellular responses of the pulmonary and hepatic phases of primary murine Schistosoma mansoni infections.

    PubMed

    Khoury, P B; Phillips, S M

    1981-03-01

    Lymphocytes from the mediastinal lymph nodes (draining the pulmonary phase of the infection), the hepatic lymph nodes (draining the hepatic phase of the infection), and the spleen of C57BL/6 mice exposed to Schistosoma mansoni were characterized relative to their capacity to interact with a soluble immunogen prepared from the adult worm (SWI). B or T RFC (rosette forming cells), RAFC (rosette-antibody forming cells), and PFC (plaque forming cells) were assayed. The RFC responses of the mediastinal and hepatic nodes were predominantly B cell in character and were maximal at that period which corresponded to the anatomic exposure which would be predicted from the migratory pattern of the parasite. High levels of T RFC and predominantly IgM B-responsive cells were generated in the mediastinal nodes during the presence of the schistosomulum in the lung parenchyma. Immunoglobulin-responsive (IgM greater than IgG greater than IgE) B cells were initially detected in the hepatic nodes during the lung-to-liver migration of the schistosomulum and its maturation to the adult form. However, elevated levels of T RFC and IgG greater than IgM greater than or equal to IgE-responsive B cells were maximally present in the hepatic nodes during optimal egg production and egg-induced granuloma formation in the liver. In contrast to the responses of the lymph nodes, the splenic responses were predominantly T cell in nature for the first 8 weeks of infection. Splenic lymphocytes expressed a biphasic response, the first represented by T RFC and IgM-responsive B cells and coincided with the migration of the schistosomulum out of the lung and the second was also represented by T RFC but with predominance of IgG-responsive B cells and correlated with the production of eggs and maximal granuloma formation at the hepatic level.

  5. Pulmonary artery sarcoma mimicking pulmonary embolism.

    PubMed

    El-Sayed Ahmed, Magdy M; Aftab, Muhammad; Al-Najjar, Raed M; de la Cruz, Kim I; Benjamin, Robert S; Hallman, Charles H

    2014-10-01

    Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival.

  6. Pulmonary Artery Sarcoma Mimicking Pulmonary Embolism

    PubMed Central

    Aftab, Muhammad; Al-Najjar, Raed M.; de la Cruz, Kim I.; Benjamin, Robert S.; Hallman, Charles H.

    2014-01-01

    Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival. PMID:25425986

  7. Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia

    PubMed Central

    2012-01-01

    Introduction Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM. Methods Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value. Results Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue r

  8. The Effect of Different Case Definitions of Current Smoking on the Discovery of Smoking-Related Blood Gene Expression Signatures in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Obeidat, Ma’en; Ding, Xiaoting; Fishbane, Nick; Hollander, Zsuzsanna; Ng, Raymond T.; McManus, Bruce; Tebbutt, Scott J.; Miller, Bruce E.; Rennard, Stephen; Paré, Peter D.

    2016-01-01

    Introduction: Smoking is the number one modifiable environmental risk factor for chronic obstructive pulmonary disease (COPD). Clinical, epidemiological and increasingly “omics” studies assess or adjust for current smoking status using only self-report, which may be inaccurate. Objective measures such as exhaled carbon monoxide (eCO) may also be problematic owing to limitations in the measurements and the relatively short half life of the molecule. In this study, we determined the impact of different case definitions of current cigarette smoking on gene expression in peripheral blood of patients with COPD. Methods: Peripheral blood gene expression from 573 former- and current-smokers with COPD in the ECLIPSE study was used to find genes whose expression was associated with smoking status. Current smoking was defined using self-report, eCO concentrations, or both. Linear regression was used to determine the association of current smoking status with gene expression adjusting for age, sex and propensity score. Pathway enrichment analyses were performed on genes with P < .001. Result: Using self-report or eCO, only two genes were differentially expressed between current and ex-smokers, with no enrichment in biological processes. When current smoking was defined using both eCO and self-report, four genes were differentially expressed (LRRN3, PID1, FUCA1, GPR15) with enrichment in 40 biological pathways related to metabolic processes, response to hypoxia and hormonal stimulus. Additionally, the combined definition provided better distributions of test statistics for differential gene expression. Conclusion: A combined phenotype of eCO and self report allows for better discovery of genes and pathways related to current smoking. Implications: Studies relying only on self report of smoking status to assess or adjust for the impact of smoking may not fully capture its effect and will lead to residual confounding of results. PMID:27154971

  9. Clinical value of whole-blood interferon-gamma assay in patients with suspected pulmonary tuberculosis and AFB smear- and polymerase chain reaction-negative bronchial aspirates.

    PubMed

    Lee, Jaehee; Lee, Shin Yup; Yoo, Seung Soo; Cha, Seung Ick; Won, Dong Il; Park, Jae Yong; Lee, Won-Kil; Kim, Chang Ho

    2012-07-01

    Combining a polymerase chain reaction (PCR) test with bronchoscopy is frequently performed to allow a rapid diagnosis of smear-negative pulmonary tuberculosis (PTB). However, limited data are available concerning clinical judgment in patients with suspected PTB and AFB smear- and PCR-negative bronchial aspirates (BA). The present study evaluated the usefulness of whole-blood QuantiFERON-TB Gold In-Tube (QFT) testing in these patients. Of 166 patients with suspected PTB who had undergone bronchoscopy because of smear-negative sputum or inadequate sputum production, 93 (56%) were diagnosed with culture-positive PTB. Seventy-four patients were either AFB smear- or PCR-positive. In the 75 patients whose BA AFB smear and PCR results were both negative, 19 were finally diagnosed with PTB by culture. The QFT test had a negative predictive value of 91% for PTB. The QFT test may be useful for excluding PTB in patients with suspected PTB whose BA AFB smear and PCR results are both negative. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Isolation and characterization of peripheral blood-derived endothelial progenitor cells from broiler chickens.

    PubMed

    Bi, Shicheng; Tan, Xun; Ali, Shah Qurban; Wei, Liangjun

    2014-11-01

    Peripheral blood-derived endothelial progenitor cells (EPCs) have been extensively studied in mammals but the isolation and characterization of EPCs in avian species have not been reported. In this study, chicken peripheral blood mononuclear cells (PBMNCs) were cultured under conditions favoring endothelial-specific differentiation for 2 weeks. One heterogeneous cell population dominated by spindle-shaped cells (early EPCs) and one homogeneous cell population exhibiting cobblestone-like morphology (endothelial outgrowth cells, EOCs) appeared sequentially. Quantitative polymerase chain reaction (PCR) showed the expression of several progenitor and endothelial cell markers such as CD133, VEGFR-2 and CD31 in both cell populations. However, CD34, another progenitor marker, was undetectable in either freshly isolated PBMNCs or cultured cells. The endothelial phenotype of the EOCs was further identified by acetylated low-density lipoprotein/lectin double staining, and in vitro tube formation. Collectively, these data demonstrate that chicken EPCs can be isolated and cultured from PBMNCs and suggest that EPCs obtained from peripheral blood may originate mainly from the CD34- subpopulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Rheological characterization of a gel produced using human blood plasma and alginate mixtures.

    PubMed

    Malagón-Romero, Dionisio; Hernández, Nicolás; Cardozo, Carmen; Godoy-Silva, Rubén D

    2014-06-01

    Human blood plasma is a material used to generate tissue equivalents due to presence of fibrinogen. However, gels formed using human blood plasma has weak mechanical properties. In this study, different mixtures of sodium alginate and blood plasma were performed and evaluated. By determining ζ potential can be established the stability of the plasma-alginate mixture and by dynamic rheology can determine the most suitable parameters for the gelation of the above mixtures, when calcium chloride is used as a crosslinker. Experimental results evidence an increment in ζ potential at alginate concentrations of 0.8% and 1.6% with a resulting pseudoplastic behavior of evaluated mixtures, which described the homogenization of the mixture. On the other hand, mixtures were gelled by using aspersion of calcium chloride and characterized by dynamic rheology. Solid behavior is dominant in all range of frequency sweep test between 0.1Hz and 100Hz. Finally, the ultimate tensile strength of a gel reach 6.36938±0.24320kPa, which is enough for manual handling of the gel. Between the tasks of the gel would be used for cell entrapment, for controlled release of drugs or in the manufacture of wound dressings.

  12. Characterization of porcine peripheral blood leukocytes by light-scattering flow cytometry.

    PubMed Central

    Wang, F I; Williams, T J; el-Awar, F Y; Pang, V F; Hahn, E C

    1987-01-01

    As a basis for other experiments using flow cytometry of porcine peripheral blood leukocytes, cell fractions were isolated by various methods and analyzed by forward angle light scatter and 90 degree light scatter. Cytospin smears of cell samples were also studied by leukocyte differential counts and nonspecific esterase staining. Three main populations of peripheral blood leukocytes [lymphocytes, monocytes, and granulocytes (primarily neutrophils)], were defined in the log 90 degree light scatter by forward angle light scatter histogram. Partial overlap was observed between lymphocyte and monocyte, and between monocyte and granulocyte domains. Correlation between leukocyte differential counts and flow cytometric quantification based on bitmap statistics of appropriate domains was between r = 0.872-0.892 for lymphocyte and granulocyte. Percoll density gradients were used for subfractionation of leukocyte populations, especially for the enrichment of granulocytes. The specific densities were calculated for lymphocytes (1.0585-1.0819 g/cc), monocytes (1.0585-1.0702 g/cc), granulocyte (1.0819-1.0936 g/cc), and erythrocytes (greater than 1.0952 g/cc). We suggest that light scatter characterization is a basis for future studies of porcine blood by flow cytometry. PMID:3453262

  13. Fabrication and characterization of 3C-silicon carbide micro sensor for wireless blood pressure measurements

    NASA Astrophysics Data System (ADS)

    Basak, Nupur

    A potentially implantable single crystal 3C-SiC pressure sensor for blood pressure measurement was designed, simulated, fabricated, characterized and optimized. This research uses a single crystal 3C-SiC, for the first time, to demonstrate its application as a blood pressure measurement sensor. The sensor, which uses the epitaxial grown 3C-SiC membrane to measure changes in pressure, is designed to be wireless, biocompatible and linear. The SiC material was chosen for its superior physical, chemical and mechanical properties; the capacitive sensor uses a 3C-SiC membrane as one of the electrodes; and, the sensor system is wireless for comfort and to allow for convenient reading of real-time pressure data (wireless communication is enabled by connecting the sensor parallel to a planar inductor). Together, the variable capacitive sensor and planar inductor create a pressure sensitive resonant circuit. The sensor system described above allows for implantation into a human patient's body, after which the planar inductor can be coupled with an external inductor to receive data for real-time blood pressure measurement. Electroplating, thick photo-resist characterization, RIE etching, oxidation, CVD, chemical mechanical polishing and wafer bonding were optimized during the process of fabricating the sensor system and, in addition to detailing the sensor system simulation and characterization; the optimized processes are detailed in the dissertation. This absolute pressure sensor is designed to function optimally within the human blood pressure range of 50-350mmHg. The layout and modeling of the sensor uses finite element analysis (FEA) software. The simulations for membrane deflection, stress analysis and electro-mechanical analysis are performed for 100 μm2 and 400μm2sensors. The membrane deflection-pressure, capacitance-pressure and resonant frequency-pressure graphs were obtained, and detailed in the dissertation, along with the planar inductor simulation for

  14. Characterization and automatic screening of reactive and abnormal neoplastic B lymphoid cells from peripheral blood.

    PubMed

    Alférez, S; Merino, A; Bigorra, L; Rodellar, J

    2016-04-01

    The objective was to advance in the automatic, image-based, characterization and recognition of a heterogeneous set of lymphoid cells from peripheral blood, including normal, reactive, and five groups of abnormal lymphocytes: hairy cells, mantle cells, follicular lymphoma, chronic lymphocytic leukemia, and prolymphocytes. A number of 4389 images from 105 patients were selected by pathologists, based on morphologic visual appearance, from patients whose diagnosis was confirmed by all the remaining complementary tests. Besides geometry, new color and texture features were extracted using six alternative color spaces to obtain rich information to characterize the cell groups. The recognition system was designed using support vector machines trained with the whole image set. In the experimental tests, individual sets of images from 21 new patients were analyzed by the trained recognition system and compared with the true diagnosis. An overall recognition accuracy of 97.67% was achieved when the cell screening was performed into three groups: normal lymphocytes, abnormal lymphoid cells, and reac