Influence of vascular enhancement, age and gender on pulmonary perfused blood volume quantified by dual-energy-CTPA

International Nuclear Information System (INIS)

Meinel, Felix G.; Graef, Anita; Sommer, Wieland H.; Thierfelder, Kolja M.; Reiser, Maximilian F.; Johnson, Thorsten R.C.

2013-01-01

Objectives: To determine the influence of technical and demographic parameters on quantification of pulmonary perfused blood volume (PBV) in dual energy computed tomography pulmonary angiography (DE-CTPA). Materials and methods: Pulmonary PBV was quantified in 142 patients who underwent DE-CTPA for suspected pulmonary embolism but in whom no thoracic pathologies were detected. Multivariate linear regression analysis was performed to calculate the influence of age, gender, enhancement of pulmonary trunk and enhancement difference between pulmonary trunk and left atrium (as a measure of timing) on PBV values. The resulting regression coefficients were used to calculate age-specific ranges of normal for PBV values adjusted for vascular enhancement and timing. Results: Enhancement of the pulmonary trunk (β = −0.29, p = 0.001) and enhancement difference between pulmonary trunk and left atrium (β = −0.24, p = 0.003) were found to significantly influence PBV values. Age (β = −0.33, p < 0.001) but not gender (β = 0.14, p = 0.05) had a significant negative influence on pulmonary PBV values. There was a 20% relative decrease of pulmonary PBV from patients aged <30 to patients over 80 years of age. Conclusions: DE-CTPA derived PBV values need to be corrected for age, vascular enhancement and timing but not for gender. The age-specific ranges of normal derived from this study can be used as a reference in future studies of PBV in pulmonary pathologies

Differential diagnosis between pulmonary tuberculosis and lung abscess by contrast enhanced CT

International Nuclear Information System (INIS)

Kanauchi, Tetsu; Hoshi, Toshiko; Konno, Miyuki; Hando, Yumiko

2001-01-01

The contrast enhanced CT findings in 14 patients with active tuberculosis and 26 patients with lung abscess were retrospectively analyzed. Reflecting the difference of pathogenesis between tuberculosis and abscess, the findings are widely different. The findings suggesting pulmonary tuberculosis rather than lung abscess were as follows; multiple and irregular necrotic areas, positive CT angiogram sign, no marginal enhancement surrounding necrosis. Contrast enhanced CT may help to distinguish pulmonary tuberculosis from lung abscess, especially in cases of caseous pneumonia showing broad consolidations or mass-like shadows. (author)

Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

DEFF Research Database (Denmark)

Christophersen, Daniel V.; Jacobsen, Nicklas R.; Andersen, Maria H. G.

2016-01-01

or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only...

In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

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Tânia A Costa

Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

Triple-phase enhanced MSCT in evaluating solitary pulmonary nodules

International Nuclear Information System (INIS)

Zhang Jin'e; Zhao Zhenjun; Liang Changhong; He Hui; Zhang Jia; Ru Guangteng

2005-01-01

Objective: An evaluation of the triple-phase enhanced MSCT in the assessment of solitary pulmonary nodules (SPN). Methods: Prospective study was made on 102 SPN using triple-phase enhanced MSCT, and the net elevation of the CT value of nodules as well as the neoplastic blood vessels were assessed. In total 102 patients were enrolled, including 63 males and 39 females, aged from 17 to 87 years (57.2 years in average). The nodules sized from 2.1 to 4.0 cm (3.3cm in average). Pulmonary carcinoma was proved in 71 cases and benign SPN in 31 cases(including 11 inflammatory pseudo tumors, 6 tuberculosis, 3 inflammatory granulomas, 3 lesions of acute nonspecific inflammation, 3 hamartomas, 3 mycosis and 2 abscesses). The spiral scan was performed on an 8-row detector spiral CT (GE/light speed Qx/I Extra) with 5mm/4 slices. The scan time was 1 second per circle. The 5mm sliced imaging was done for CT value measurement and 1.25mm sliced imaging was for MPR(multiplanar reconstruction) or VR(volume rendering), 20ml Ultravist(300 mg/I) was administered at first at a rate of 4ml/s via forearm superficial vein by a power injector. The peak CT values in pulmonary artery and aorta were to determine the delay time for the acquisition in pulmonary phase and aortal phase. Then Ultravist in a volume of lml/ body kilogram was injected, followed by 50 ml of sodium chloride. Delay phase was 3 minutes. Results: The differences of net increased CT value in three phases were statistically significant respectively between lung cancer and benign nodules (F=30.668, 4.495 and 56.141, respectively, P=0.000, 0.036 and 0. 000, respectively). When the net increased CT value≥20 HU was set as a diagnostic threshold, the sensitivity, specificity, positive predict value, negative predict value and veracity were 93%, 29%, 75%, 64.3% and 73.5%. When net increased CT value ≥20 HU in aortal phase while net increased CT value < 20 HU in pulmonary phase was set as a di- agnostic threshold, those values

Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

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Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

2016-01-01

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

Regional distribution of ventilation and perfusion in patients with obstructive pulmonary disease and alpha/sub 1/-antitrypsin deficiency

Energy Technology Data Exchange (ETDEWEB)

Mostafa, A B.M.G.; Tulley, N J; Harding, L K; Stockley, R A

1983-08-01

Regional distribution of pulmonary ventilation and perfusion has been determined of 13 patients with chronic obstructive pulmonary disease (COPD). Eight patients had alpha/sub 1/-antitrypsin deficiency (..cap alpha../sub 1/ATD). Ventilation studies were carried out using xenon-133 (/sup 133/Xe) and krypton-81m (sup(81m)Kr) gases. Trapping indices were determined from the wash-out part of the xenon ventilation studies. Results obtained from patients were compared with those of normal controls. Ventilation studies with sup(81m)Kr showed pulmonary changes more clearly than did /sup 133/Xe studies and the trapping of radio-xenon was more extensive in lung bases than in apices whether or not the patients had ..cap alpha../sub 1/ ATD. The distribution of perfusion followed a pattern similar to that of ventilation, but did not differ statistically from that of the normal controls.

Phosphorus deficiency enhances molybdenum uptake by tomato plants

International Nuclear Information System (INIS)

Heuwinkel, H.; Kirkby, E.A.; Le Bot, J.; Marschner, H.

1992-01-01

Water culture experiments are described which provide conclusive evidence that Mo uptake by tomato plants is markedly enhanced by P deficiency. In a longterm experiment, which ran for 11 days, in marked contrast to the uptake of other nutrients, a three fold higher Mo uptake rate was observed after only four days of withdrawal of P from the nutrient medium. In contrast to the gradual increase in pH of the nutrient medium of the plants supplied with P, the pH in the medium of the -P plants fell. Throughout the growth of these plants net H+ efflux could be accounted for by excess cation over anion uptake, indicating that organic acid extrusion plays no major role in the observed fall in pH. Further evidence that Mo uptake is enhanced in P deficient tomato plants is provided in short-term nutrient solution experiments (1h and 4h) using radioactive molybdenum (99Mo). Compared with P sufficient plants, the uptake rates of 99Mo by P deficient plants were three to five times higher after 1h and nine to twelve times higher after 4h. Resupplying P during the uptake periods to deficient plants reduced the uptake rate of 99Mo to values similar to those of P sufficient plants. It is concluded that the uptake of molybdate occurs via phosphate binding/ transporting sites at the plasma membrane of root cells. Further support for this conclusion comes from exchange experiments with non-labelled molybdenum, which show a much larger amount of 99Mo exchangeable from the roots of P deficient plants

Caspase-11 Plays a Protective Role in Pulmonary Acinetobacter baumannii Infection.

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Wang, Wei; Shao, Yue; Li, Shengjun; Xin, Na; Ma, Tingxian; Zhao, Chenghai; Song, Min

2017-10-01

Activation of caspase-11 by some Gram-negative bacteria triggers the caspase-1/interleukin 1β (IL-1β) pathway, independent of canonical inflammasomes. Acinetobacter baumannii is a Gram-negative, conditionally pathogenic bacterium that can cause severe pulmonary infection in hospitalized patients. A. baumannii was revealed to activate canonical and noncanonical inflammasome pathways in bone marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11 -/- mice with A. baumannii showed that caspase-11 deficiency impaired A. baumannii clearance, exacerbated pulmonary pathological changes, and enhanced susceptibility to A. baumannii These data indicate that the caspase-11-mediated innate immune response plays a crucial role in defending against A. baumannii . Copyright © 2017 American Society for Microbiology.

Assessment of pulmonary ventilation patterns by nonradioactive Xe enhanced CT

International Nuclear Information System (INIS)

Shiraishi, Tomokuni; Mizuno, Masayoshi; Harima, Yoko; Kobayashi, Akitomo; Hasegawa, Takeo

1984-01-01

To assess the patterns of regional pulmonary ventilation in conjunction with pulmonary blood flow, pulmonary Xe enhanced CT was performed in 26 patients with interstitial disorders including 3 with chest irradiation and 23 with old myocardial infarction and in 2 control patients. Washout time was short and its patterns were not influenced by an increased or decreased blood flow in the control group. In the group with chest irradiation, a decreased blood flow and slight disturbance were seen in the affected lung, while an increased blood flow and a slightly increased resistance of the pulmonary periphery were suspected in the opposite lung. Furthermore, a prolonged washout and relative reduction of the washout seemed to be reflective of the interstitial degeneration and decreased blood flow, respectively. In the group with old myocardial infarction, the prolongation of washout became marked because of a decreased blood flow caused by venous congestion. (Namekawa, K.)

Biotin deficiency enhances the inflammatory response of human dendritic cells.

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Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

2016-09-01

The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

Pulmonary CT angiography: optimization of contrast enhancement technique

International Nuclear Information System (INIS)

Ma Lianju; Tang Guangjian; Fu Jiazhen

2012-01-01

Objective: To derive and evaluate the formula of exactly calculating the contrast dosage used during pulmonary CT angiography (CTPA). Methods: Time density curves in 27 patients who underwent CTPA were collected and analyzed,the formula for calculating contrast dosage during CTPA was derived. 68 patients suspected of pulmonary embolism (PE) clinically but no PE on CTPA were divided randomly into group A, with bolus tracing technique (n=26), and group B, with small dose injection contrast test (SDCT) (n=42). The CT values of the right main pulmonary artery (RMPA), right upper pulmonary vein (RUPV), right posterior basal PA, right lower PV (RLPV) and the aorta were calculated. The total contrast dosage and the hard beam artifact in the SVC were compared between the two groups.Student's t test, Chi-square test and Mann-Whitney U test were used. Results: The ratio of the time from starting injection to enhancement peak of caudal end of SVC and the time to enhancement peak of the main pulmonary trunk was 0.65 ±0.09 (about 2/3), the formula for contrast dosage calculation was derived as (DTs/3 + STs/2) FR ml/s. The CT values of RMPA and RLPA between the two groups [(301 ±117), (329 ± 122) and (283 ±95), (277 ±98) HU respectively] were not significantly different (t=1.060, P=0.292; t=2.056, P=0.044), but the differences of CT values in the paired PA and PV between the two groups (median were 22.5, 58.0 and 170.5, 166.5 HU respectively) were significant (U=292, P=0.001 and U=325, P=0.005), contrast artifact of the SVC (grade 1-3) in group B (n=34, 7, 1 respectively) was significantly less than in group A (n=11, 10, 5 respectively, χ 2 =10.714, P=0.002), the contrast dosage injected in group A was ( 87.6 ± 7.3) ml, and in group B was (40.0 ±5.4) ml (P<0.01). Conclusion: CTPA with SDCT technique is superior to that with conventional bolus tracing technique regarding contrast dosage and contrast artifact in the SVC. (authors)

Tuberculosis and the acquired immune deficiency syndrome in South Brazil

International Nuclear Information System (INIS)

Vieira, M.V.; Genro, C.H.; Santos Silveira, R. de C. dos

1989-01-01

Tuberculosis and the acquired immune deficiency syndrome in South Brazil. The authors studied the incidence of tuberculosis in South Brazilian patients with acquired immune deficiency syndrome from January 1985 to June 1988. During this period, tuberculosis occurred in 10.3% of acquired immune deficiency syndrome patients. The socioeconomic conditions and the incidence of disease in the population were not confirmed as a potential risk for tuberculosis infection. Chest radiographs revealed pulmonary infiltrates in six patients, hilar and/or mediastinal adenopathy in three, and pleural effusion in two. The two remaining patients had pulmonary consolidation associated with other features. None of these patients presented pulmonary cavitation or radiographic findings of typical reactivation of pulmonary tuberculosis. (author) [pt

Pulmonary arterial lesions in explanted lungs after transplantation correlate with severity of pulmonary hypertension in chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Carlsen, Jørn; Andersen, Kasper Hasseriis; Boesgaard, Søren

2013-01-01

BACKGROUND: Pulmonary vascular findings are largely unreported in end-stage chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary vascular lesions in explanted lungs from 70 patients with COPD/emphysema or α-1-antitrypsin deficiency were analyzed retrospectively. Patients were stratified...... of pulmonary vascular lesions in COPD correlate with the severity of PH. Morphologic lesions similar to those characteristic of IPAH can be observed as PH in COPD progresses to levels characteristic of IPAH....... by the presence and severity of pulmonary hypertension (PH) assessed by right-heart catheterization in 3 hemodynamically distinct groups: (1) non-PH (mean pulmonary arterial pressure [mPAP]50 mm Hg; median HE Grade 4 (range 3-6), with generalized arterial dilatation and plexiform lesions. CONCLUSIONS: The extent...

Intermittent hypoxia and hypercapnia induce pulmonary artery atherosclerosis and ventricular dysfunction in low density lipoprotein receptor deficient mice.

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Douglas, Robert M; Bowden, Karen; Pattison, Jennifer; Peterson, Alexander B; Juliano, Joseph; Dalton, Nancy D; Gu, Yusu; Alvarez, Erika; Imamura, Toshihiro; Peterson, Kirk L; Witztum, Joseph L; Haddad, Gabriel G; Li, Andrew C

2013-12-01

Patients with obstructive sleep apnea, who experience episodic hypoxia and hypercapnia during sleep, often demonstrate increased inflammation, oxidative stress, and dyslipidemia. We hypothesized that sleep apnea patients would be predisposed to the development of atherosclerosis. To dissect the mechanisms involved, we developed an animal model in mice whereby we expose mice to intermittent hypoxia/hypercapnia (IHH) in normobaric environments. Two- to three-month-old low-density lipoprotein receptor deficient (Ldlr(-/-)) mice were fed a high-fat diet for 8 or 16 wk while being exposed to IHH for either 10 h/day or 24 h/day. Plasma lipid levels, pulmonary artery and aortic atherosclerotic lesions, and cardiac function were then assayed. Surprisingly, atherosclerosis in the aorta of IHH mice was similar compared with controls. However, in IHH mice, atherosclerosis was markedly increased in the trunk and proximal branches of the pulmonary artery of exposed mice; even though plasma cholesterol and triglycerides were lower than in controls. Hemodynamic analysis revealed that right ventricular maximum pressure and isovolumic relaxation constant were significantly increased in IHH exposed mice and left ventricular % fractional shortening was reduced. In conclusion, 1) Intermittent hypoxia/hypercapnia remarkably accelerated atherosclerotic lesions in the pulmonary artery of Ldlr(-/-) mice and 2) increased lesion formation in the pulmonary artery was associated with right and left ventricular dysfunction. These findings raise the possibility that patients with obstructive sleep apnea may be susceptible to atherosclerotic disease in the pulmonary vasculature, an observation that has not been previously recognized.

Qualitative indices and enhancement rate of CT pulmonary angiography in patients with suspected pulmonary embolism: Comparison between test bolus and bolus-tracking methods

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Maryam Moradi

2016-01-01

Full Text Available Background: The aim of the present study was to assess the qualitative indices and enhancement rate of computed tomographic pulmonary angiography (CTPA in patients with suspected pulmonary embolism using Test bolus and Bolus-tracking techniques. Materials and Methods: Fifty-two patients with suspected pulmonary embolism that passed informed consent were randomly divided in the two groups. In each group, demographic characteristics, qualitative indices, and enhancement rate of CTPA were recorded. Results: The diagnostic result obtained in majority of the participants in the two groups (88.5 % in Test bolus group vs. 73.1% in the Bolus tracking group. In the case of quantitative variables, no statistically significant differences were found between the groups (P > 0.05. The only statistically significant difference between the two groups is average of "X-ray dose". Conclusion: The results of our study show that there is no statistically significant difference between the Bolus Tracking and Test Bolus techniques for producing more homogeneous enhancement.

Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

Science.gov (United States)

Chono, Sumio; Togami, Kohei; Itagaki, Shirou

2017-11-01

We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

OpenAIRE

Pfister, Sandra L.

2011-01-01

Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

Intermittent hypoxia and hypercapnia induce pulmonary artery atherosclerosis and ventricular dysfunction in low density lipoprotein receptor deficient mice

Science.gov (United States)

Bowden, Karen; Pattison, Jennifer; Peterson, Alexander B.; Juliano, Joseph; Dalton, Nancy D.; Gu, Yusu; Alvarez, Erika; Imamura, Toshihiro; Peterson, Kirk L.; Witztum, Joseph L.; Haddad, Gabriel G.; Li, Andrew C.

2013-01-01

Patients with obstructive sleep apnea, who experience episodic hypoxia and hypercapnia during sleep, often demonstrate increased inflammation, oxidative stress, and dyslipidemia. We hypothesized that sleep apnea patients would be predisposed to the development of atherosclerosis. To dissect the mechanisms involved, we developed an animal model in mice whereby we expose mice to intermittent hypoxia/hypercapnia (IHH) in normobaric environments. Two- to three-month-old low-density lipoprotein receptor deficient (Ldlr−/−) mice were fed a high-fat diet for 8 or 16 wk while being exposed to IHH for either 10 h/day or 24 h/day. Plasma lipid levels, pulmonary artery and aortic atherosclerotic lesions, and cardiac function were then assayed. Surprisingly, atherosclerosis in the aorta of IHH mice was similar compared with controls. However, in IHH mice, atherosclerosis was markedly increased in the trunk and proximal branches of the pulmonary artery of exposed mice; even though plasma cholesterol and triglycerides were lower than in controls. Hemodynamic analysis revealed that right ventricular maximum pressure and isovolumic relaxation constant were significantly increased in IHH exposed mice and left ventricular % fractional shortening was reduced. In conclusion, 1) Intermittent hypoxia/hypercapnia remarkably accelerated atherosclerotic lesions in the pulmonary artery of Ldlr−/− mice and 2) increased lesion formation in the pulmonary artery was associated with right and left ventricular dysfunction. These findings raise the possibility that patients with obstructive sleep apnea may be susceptible to atherosclerotic disease in the pulmonary vasculature, an observation that has not been previously recognized. PMID:23990245

The feasibility and accuracy of enhanced MR pulmonary perfusion imaging in evaluating therapeutic effect of pulmonary embolism

International Nuclear Information System (INIS)

Wang Nana; Lv Biao; Zhao Zhaoqi; Huang Xiaoyong; Lu Dongxu; Mi Hongzhi; Yu Weiyong

2010-01-01

Objective: To investigate the feasibility and accuracy of enhanced magnetic resonance pulmonary perfusion imaging (MRPP) in the diagnosis and follow-up of pulmonary embolism (PE). Methods: Sixty patients suspected of PE underwent MRPP. Twenty-seven patients also underwent radionuclide perfusion imaging. 22 patients repeated MRPP examination after 3 day to 1 month antieoagulation or thrombolytic therapy. The feasibility and accuracy of MRPP in the diagnosis and follow-up of PE were evaluated according to the transformation rate of signal (TROS), time-signal curve and some parameters of main pulmonary artery (such as peak value of flow, mean flow velocity and flow rate). The t test and rank sum test were used for the statistics. Results: MRPP showed a high agreement with radionuclide perfusion imaging. TROS was (2.86 ± 2.48) vs(6.72 ± 2.54) (t=3.370, P 0.05). Conclusion: MRPP shows a high agreement with radionuclide perfusion imaging and is a useful method for the diagnosis and follow-up of PE. (authors)

Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats

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Holmes Amey J

2005-07-01

Full Text Available Abstract Background Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA or remained unsupplemented. Methods Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion. Results VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment. Conclusion Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.

MDCT evaluation of pulmonary embolism in children and young adults following a lateral tunnel Fontan procedure: optimizing contrast-enhancement techniques

International Nuclear Information System (INIS)

Prabhu, Sanjay P.; Mahmood, Soran; Sena, Laureen; Lee, Edward Y.

2009-01-01

Pulmonary embolism (PE) is a life-threatening thromboembolic complication in patients who have undergone a Fontan procedure for augmenting pulmonary blood flow in the setting of single-ventricle physiology. In patients following a Fontan procedure, lack of proper contrast agent mixing in the right atrium and sluggish, low-velocity blood flow within the Fontan circulation often results in suboptimal contrast enhancement within the pulmonary artery for evaluating PE. Unfortunately, there is a paucity of information describing the optimal contrast-enhancement technique with multidetector CT (MDCT) for evaluating PE in children and young adults following a Fontan procedure. We illustrate the MDCT imaging findings of suboptimal contrast enhancement within the pulmonary artery, which can be mistaken for PE, in patients following a lateral Fontan procedure, and we discuss MDCT techniques to optimize contrast enhancement within the pulmonary artery in these patients for evaluating PE. The MDCT imaging findings in pediatric and young adult patients following a lateral Fontan procedure and with clinically suspected PE are illustrated. We describe intravenous contrast agent injection techniques that can be used to optimize the contrast enhancement in the pulmonary artery in patients following a lateral Fontan procedure. The use of a suboptimal contrast-enhancement technique led to initial misdiagnosis and incomplete evaluation of PE in the three patients following a lateral Fontan procedure. Imaging in two patients showed that optimal evaluation of thrombosis in the Fontan pathway and PE in the pulmonary arteries can be successfully achieved with simultaneous upper- and lower-limb injections of contrast agent. This series demonstrates that suboptimal contrast enhancement can result in misdiagnosis or incomplete evaluation of PE in children and young adults following a lateral Fontan procedure. Careful attention to optimizing contrast enhancement during MDCT examination for

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

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Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

2013-01-01

SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

MURC deficiency in smooth muscle attenuates pulmonary hypertension.

Science.gov (United States)

Nakanishi, Naohiko; Ogata, Takehiro; Naito, Daisuke; Miyagawa, Kotaro; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Kasahara, Takeru; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

2016-08-22

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.

Assessment of chronic thromboembolic pulmonary hypertension by three-dimensional contrast-enhanced MR angiography - comparison with selective intraarterial DSA

International Nuclear Information System (INIS)

Kreitner, K.F.; Ley, S.; Kauczor, H.U.; Kalden, P.; Pitton, M.B.; Thelen, M.; Mayer, E.; Laub, G.

2000-01-01

Purpose: This study compares contrast-enhanced 3D-MR angiography (MRA) of the pulmonary arteries with selective intraarterial DSA in patients with chronic thromboembolic pulmonary hypertension. Materials and methods: 20 patients preoperatively underwent a contrast-enhanced 3D-MRA of the pulmonary arteries at 1.5 T using the phased-array body coil. For MRA, we used a 3D-Flash-sequence after bolus timing. 2 radiologists analyzed the acquired image material in consensus with respect to the detection of central thromboembolic material and the visualization of the pulmonary arterial tree. Finally, the MR angiograms were compared with selective DSA images using surgical findings as the definitive standard. Results: MRA demonstrated central thromboembolic material, vessel cut-offs and abnormal proximal-to-distal tapering in all patients. Compared to DSA, MRA depicted the pulmonary vessels up to the segmental level in all cases, it was inferior to DSA in delineation of the subsegmental arteries (sensitivity 87%, specificity 100%). The central beginning of the thromboembolic occlusions seen at MRA corresponded to the beginning of the deobliteration procedure during pulmonary thromboendarterectomy in every case. (orig.) [de

Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.

Science.gov (United States)

Pfister, Sandra L

2011-04-01

Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.

The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

International Nuclear Information System (INIS)

Park, J.E.S.; Beal, I.; Dilworth, J.P.; Tormey, V.; Haddock, J.

2005-01-01

Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly

The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

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Park, J.E.S. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Beal, I. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Dilworth, J.P. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Tormey, V. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Haddock, J. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom)]. E-mail: jamandahaddock@royalfree.nhs.uk

2005-06-01

Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.

Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

Science.gov (United States)

Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

2009-02-01

Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

{sup 18}F-FDG PET/CT and contrast-enhanced CT findings of pulmonary cryptococcosis

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Wang, Si-yun, E-mail: wang_shuxia@outlook.com [Department of PET Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Chen, Gang, E-mail: cgggh@outlook.com [Department of Thoracic Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Luo, Dong-lan, E-mail: 695532870@qq.com [Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Shao, Dan, E-mail: shaodan501@outlook.com [Department of PET Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Liu, En-tao, E-mail: GDGH2015@gmail.com [Department of PET Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Sun, Taotao, E-mail: sunmoodsdaisy@bjmu.edu.cn [Department of PET Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China); Wang, Shu-Xia, E-mail: wsyggh@outlook.com [Department of PET Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China)

2017-04-15

Purpose: Pulmonary cryptococcosis is an uncommon cause of pulmonary nodules in non-AIDS patients. This study reports the {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET/CT) and contrast-enhanced CT (CE-CT) findings of 42 patients with pulmonary cryptococcosis. Materials and methods: A retrospective review of the {sup 18}F-FDG PET/CT and CE-CT findings of 42 patients with histologically proven pulmonary cryptococcosis was conducted. All patients underwent PET/CT and CE-CT in the same session. The CT diagnosis was based on the location, morphological features, and enhancement of lesions. The PET/CT findings were recorded, and clinical data and surgical and histopathological findings were collected. Results: The results of the PET scans revealed that 37 (88%) of 42 patients showed higher FDG uptake, and 5 (12%) patients demonstrated lower FDG uptake than the mediastinal blood pool. The maximum standardized uptake value (SUV) of pulmonary cryptococcosis ranged from 1.4 to 13.0 (average: 5.7 ± 3.3, median 4.9). A single nodular pattern was the most prevalent pattern observed and was found in 29 (69%) patients. This pattern was followed by scattered nodular (n = 4, 10%), clustered nodular (n = 3, 7%), mass-like (n = 3, 7%), and bronchopneumonic (n = 3, 7%) patterns. The most frequent pattern of immunocompetent patients was the single nodular pattern (29 of 33, 88%). Immunocompromised patients most frequently pattern exhibited mass-like (3 of 9, 33%) and bronchopneumonic (3 of 9, 33%) patterns. Conclusion: Pulmonary cryptococcosis most commonly appears as single nodules in immunocompetent patients. Mass-like and bronchopneumonic patterns were common in immunocompromised patients. In 88% of patients, lung lesions showed high FDG uptake, thus mimicking a possible malignant condition.

Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

International Nuclear Information System (INIS)

Hiraki, T.; Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

2004-01-01

A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred

Contrast-enhanced magnetic resonance imaging of pulmonary lesions: Description of a technique aiming clinical practice

International Nuclear Information System (INIS)

Koenigkam-Santos, Marcel; Optazaite, Elzbieta; Sommer, Gregor; Safi, Seyer; Heussel, Claus Peter; Kauczor, Hans-Ulrich

2015-01-01

To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Material and methods: Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Results: Readers agreed moderately to substantially concerning lesions’ enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. Conclusions: The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions

Contrast-enhanced magnetic resonance imaging of pulmonary lesions: Description of a technique aiming clinical practice

Energy Technology Data Exchange (ETDEWEB)

Koenigkam-Santos, Marcel, E-mail: marcelk46@yahoo.com.br [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Radiology Department, German Cancer Research Center (Deutsches Krebsforschungszentrum – DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Radiology, University Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, Campus Universitario Monte Alegre, 14048 900 Ribeirao Preto, Sao Paulo (Brazil); Optazaite, Elzbieta, E-mail: optazaite@andrulis.eu [Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Sommer, Gregor, E-mail: gregor.sommer@usb.ch [Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Safi, Seyer, E-mail: seyer.safi@gmail.com [Surgery Department, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Heussel, Claus Peter, E-mail: heussel@uni-heidelberg.de [Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich, E-mail: hans-ulrich.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); and others

2015-01-15

To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Material and methods: Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Results: Readers agreed moderately to substantially concerning lesions’ enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. Conclusions: The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions.

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

Science.gov (United States)

Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

2008-10-01

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

Oxygen-enhanced MRI vs. quantitatively assessed thin-section CT: Pulmonary functional loss assessment and clinical stage classification of asthmatics

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Koyama, Hisanobu; Matsumoto, Keiko; Onishi, Yumiko; Nogami, Munenobu; Takenaka, Daisuke; Matsumoto, Sumiaki; Sugimura, Kazuro

2011-01-01

Purpose: The purpose of this study was to prospectively compare the efficacy of oxygen-enhanced MR imaging (O 2 -enhanced MRI) and CT for pulmonary functional loss assessment and clinical stage classification of asthmatics. Materials and methods: O 2 -enhanced MRI, CT and %FEV 1 measurement were used 34 consecutive asthmatics classified into four stages ('Mild Intermittent [n = 7]', 'Mild Persistent [n = 8], 'Moderate Persistent [n = 14]' and 'Severe Persistent [n = 5]'). Relative enhancement ratio maps for every subject were generated, and determine mean relative enhancement ratios (MRERs). Mean lung density (MLD) and the airway wall area (WA) corrected by body surface area (WA/BSA) were also measured on CT. To compare the efficacy of the two methods for pulmonary functional loss assessment, all indexes were correlated with %FEV 1 . To determine the efficacy of the two methods for clinical stage classification, all parameters for the four clinical stages were statistically compared. Results: %FEV 1 showed fair or moderate correlation with all parameters (0.15 ≤ r 2 ≤ 0.30, p 2 -enhanced MRI is as effective as CT for pulmonary functional loss assessment and clinical stage classification of asthmatics.

Primary pulmonary low-grade angiosarcoma characterized by mismatch between {sup 18}F-FDG FET and dynamic contrast-enhanced CT

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KIm, Eun Young; Lee, Ho Yun; Han, Joung Ho; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2015-10-15

We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an {sup 18}F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.

Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

International Nuclear Information System (INIS)

Bessa, Luiz Gustavo Pignataro; Junqueira, Flávia Pegado; Bandeira, Marcelo Luiz da Silva; Garcia, Marcelo Iorio; Xavier, Sérgio Salles; Lavall, Guilherme; Torres, Diego; Waetge, Daniel

2013-01-01

Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m 2 , and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m 2 , there was a relevant association with the increased percentage of myocardial fibrosis. The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension

Pulmonary Arterial Hypertension: Use of Delayed Contrast-Enhanced Cardiovascular Magnetic Resonance in Risk Assessment

Energy Technology Data Exchange (ETDEWEB)

Bessa, Luiz Gustavo Pignataro, E-mail: lgpignataro@ig.com.br; Junqueira, Flávia Pegado; Bandeira, Marcelo Luiz da Silva; Garcia, Marcelo Iorio; Xavier, Sérgio Salles; Lavall, Guilherme; Torres, Diego; Waetge, Daniel [Hospital Universitário Clementino Fraga Filho, Ilha do Fundão, RJ (Brazil)

2013-10-15

Pulmonary arterial hypertension is a severe and progressive disease. Its early diagnosis is the greatest clinical challenge. To evaluate the presence and extension of the delayed myocardial contrast-enhanced cardiovascular magnetic resonance, as well as to verify if the percentage of the myocardial fibrosis mass is a severity predictor. Cross-sectional study with 30 patients with pulmonary arterial hypertension of groups I and IV, subjected to clinical, functional and hemodynamic evaluation, and to cardiac magnetic resonance. The mean age of patients was 52 years old, with female predominance (77%). Among the patients, 53% had right ventricular failure at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute walk test was 395m. In hemodynamic study with right catheterism, the mean average pulmonary arterial pressure was 53.3mmHg, of the cardiac index of 2.1L/ min.m{sup 2}, and median right atrial pressure was 13.5 mmHg. Delayed myocardial contrast enhanced cardiovascular magnetic resonance was found in 28 patients. The mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was 6.17%. The presence of functional class IV, right ventricular failure at diagnosis, 6-minute walk test < 300 meters and right atrial pressure ≥ 15 mmHg, with cardiac index < 2.0 L/ min.m{sup 2}, there was a relevant association with the increased percentage of myocardial fibrosis. The percentage of the myocardial fibrosis mass indicates a non-invasive marker with promising perspectives in identifying patients with high risk factors for pulmonary hypertension.

Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

Energy Technology Data Exchange (ETDEWEB)

Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nakagami-Gun, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

2014-02-15

Purpose: To prospectively and directly compare oxygen-enhanced (O{sub 2}-enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O{sub 2}-enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O{sub 2}-enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O{sub 2}-enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD.

Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Tsubakimoto, Maho; Sugimura, Kazuro

2014-01-01

Purpose: To prospectively and directly compare oxygen-enhanced (O 2 -enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O 2 -enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O 2 -enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O 2 -enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD

Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

Directory of Open Access Journals (Sweden)

Jain PP

2014-07-01

Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy.

Science.gov (United States)

Walts, Ann E; Bomalaski, John S; Ines, Delma; Orsulic, Sandra

2015-08-01

Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors including small cell lung cancer (SCLC). We sought to assess ASS expression in a cohort of high-grade pulmonary neuroendocrine carcinomas (PNEC) which include SCLC and large cell neuroendocrine carcinoma (LCNEC). Sixty-nine PNEC (49 SCLC and 20 LCNEC) were retrieved from our pathology archives. Formalin-fixed paraffin-embedded sections of the 54 primary tumors, 15 metastases and appropriate positive and negative controls were immunostained using an ASS-specific monoclonal antibody. Positive staining in ASS negative. 58 % of the PNEC including 61.2 % of the SCLC and 50 % of the LCNEC were ASS negative. These ASS-negative tumors included 63 % of the primary and 40 % of the metastatic lesions tested. More than 50 % of the high-grade PNEC tested lack immunohistochemically detectable ASS, suggesting that they are auxotrophic for arginine and potential candidates for arginine deprivation therapy. PNEC comprise about 25 % of primary lung cancers and have a 5-year overall survival of only 5-10 %, underscoring the need for new and more effective therapies. Immunostaining for ASS has potential to improve the selection of patients with PNEC for arginine deprivation therapy with ADI-PEG 20.

Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

International Nuclear Information System (INIS)

Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille; Dadrich, Monika; Hauser, Kai; Abdollahi, Amir; Groene, Hermann-Josef; Angel, Peter; Huber, Peter E.

2010-01-01

Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results: We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.

Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

Science.gov (United States)

Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

2016-01-01

Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension

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Rajaram, Smitha [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Sheffield (United Kingdom); Swift, Andrew J.; Wild, Jim M. [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Sheffield Cardiovascular Biomedical Research Unit, Sheffield (United Kingdom); Capener, David; Telfer, Adam [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Davies, Christine; Hill, Catherine [Sheffield Teaching Hospitals Trust, Department of Radiology, Sheffield (United Kingdom); Condliffe, Robin; Elliot, Charles; Kiely, David G. [Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (United Kingdom); Sheffield Cardiovascular Biomedical Research Unit, Sheffield (United Kingdom); Hurdman, Judith [Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (United Kingdom)

2012-02-15

To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography compared with CT pulmonary angiography (CTPA) in patients with chronic thromboembolic disease (CTE). A 2 year retrospective study of 53 patients with chronic thromboembolic pulmonary hypertension who underwent CTPA and MRI for suspected pulmonary hypertension and a control group of 36 patients with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined. CE-MRA generated lung perfusion maps were also assessed. The overall sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were 98% and 94%, respectively. The sensitivity improved from 50% to 88% for central vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a sensitivity of 92% for diagnosing CTE. CE-MRA has high sensitivity and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation of adherent central and lobar thrombus significantly improves with the addition of unenhanced proton MRA which delineates the vessel wall. (orig.)

Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension

International Nuclear Information System (INIS)

Rajaram, Smitha; Swift, Andrew J.; Wild, Jim M.; Capener, David; Telfer, Adam; Davies, Christine; Hill, Catherine; Condliffe, Robin; Elliot, Charles; Kiely, David G.; Hurdman, Judith

2012-01-01

To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography compared with CT pulmonary angiography (CTPA) in patients with chronic thromboembolic disease (CTE). A 2 year retrospective study of 53 patients with chronic thromboembolic pulmonary hypertension who underwent CTPA and MRI for suspected pulmonary hypertension and a control group of 36 patients with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined. CE-MRA generated lung perfusion maps were also assessed. The overall sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were 98% and 94%, respectively. The sensitivity improved from 50% to 88% for central vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a sensitivity of 92% for diagnosing CTE. CE-MRA has high sensitivity and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation of adherent central and lobar thrombus significantly improves with the addition of unenhanced proton MRA which delineates the vessel wall. (orig.)

Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

Science.gov (United States)

Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

2014-10-01

The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

Benign pulmonary nodule. Morphological features and contrast enhancement evaluated with contiguous thin-section CT

Energy Technology Data Exchange (ETDEWEB)

Matsuo, Hisayasu; Murata, Kiyoshi; Takahashi, Masashi; Morita, Rikushi [Shiga Univ. of Medical Science, Otsu (Japan)

1998-10-01

The morphological changes in 54 benign lung nodules, including 8 histologically proven nodules of tuberculoma, 10 of focal organizing pneumonia (FOP), 1 of lung abscess and 35 other benign nodules, were evaluated with contiguous thin-section (3 mm) CT. In addition, incremental dynamic studies were carried out in 25 of these nodules. The three-dimensional shapes of the nodules were found to be quite varied and were classified into four types: round mass (n=18), polygonal mass with concave or straight margins (n=20), oval or band-like mass extending along the bronchovascular bundle (n=7), and oval mass attached to the pleura with broad contact (n=9). Forty-two (78%) of the 54 nodules were located along the bronchovascular bundle. The maximum increments in CT values over 20 HU were observed after contrast enhancement in 18 (72%) of the 25 benign nodules, among which all tuberculomas showed little or no contrast enhancement. The number of small vessels quantified microscopically in the center of the nodules were minimal in tuberculomas with little enhancement and plentiful in lesions of FOP and abscess which showed marked enhancement. Our results suggest that the differentiation between benign and malignant pulmonary nodules is not possible simply on the basis of the degree of contrast enhancement. Therefore, morphological features and the anatomical relation to the bronchovascular bundles should also be taken into consideration in the diagnosis of pulmonary nodules. (author)

Benign pulmonary nodule. Morphological features and contrast enhancement evaluated with contiguous thin-section CT

International Nuclear Information System (INIS)

Matsuo, Hisayasu; Murata, Kiyoshi; Takahashi, Masashi; Morita, Rikushi

1998-01-01

The morphological changes in 54 benign lung nodules, including 8 histologically proven nodules of tuberculoma, 10 of focal organizing pneumonia (FOP), 1 of lung abscess and 35 other benign nodules, were evaluated with contiguous thin-section (3 mm) CT. In addition, incremental dynamic studies were carried out in 25 of these nodules. The three-dimensional shapes of the nodules were found to be quite varied and were classified into four types: round mass (n=18), polygonal mass with concave or straight margins (n=20), oval or band-like mass extending along the bronchovascular bundle (n=7), and oval mass attached to the pleura with broad contact (n=9). Forty-two (78%) of the 54 nodules were located along the bronchovascular bundle. The maximum increments in CT values over 20 HU were observed after contrast enhancement in 18 (72%) of the 25 benign nodules, among which all tuberculomas showed little or no contrast enhancement. The number of small vessels quantified microscopically in the center of the nodules were minimal in tuberculomas with little enhancement and plentiful in lesions of FOP and abscess which showed marked enhancement. Our results suggest that the differentiation between benign and malignant pulmonary nodules is not possible simply on the basis of the degree of contrast enhancement. Therefore, morphological features and the anatomical relation to the bronchovascular bundles should also be taken into consideration in the diagnosis of pulmonary nodules. (author)

Perfusion redistribution after a pulmonary-embolism-like event with contrast enhanced EIT.

Science.gov (United States)

Nguyen, D T; Bhaskaran, A; Chik, W; Barry, M A; Pouliopoulos, J; Kosobrodov, R; Jin, C; Oh, T I; Thiagalingam, A; McEwan, A L

2015-06-01

Recent studies showed that regional pulmonary perfusion can be reliably estimated using electrical impedance tomography (EIT) with the aid of hypertonic saline based contrast enhancement. Building on these successful studies, we studied contrast EIT for pulmonary perfusion defect caused by an artificially induced pulmonary embolism (PE) in a large ovine model (N = 8, 78 ± 7.8 kg). Furthermore, the efficacy of a less invasive contrast bolus of 0.77 ml kg(-1) of NaCl 3% was compared with a more concentrated bolus of 0.13 ml kg(-1) of NaCl 20%. Prior to the injection of each contrast bolus injection, ventilation was turned off to provide a total of 40 to 45 s of apnoea. Each bolus of impedance contrast was injected through a catheter into the right atrium. Pulmonary embolisation was performed by balloon occlusion of part of the right branch of the pulmonary trunk. Four parameters representing the kinetics of the contrast dilution in the lung were evaluated for statistical differences between baseline and PE, including peak value, maximum uptake, maximum washout and area under the curve of the averaged contrast dilution curve in each lung. Furthermore, the right lung to left lung (R2L) ratio of each the aforementioned parameters were assessed. While all of the R2L ratios yielded significantly different means between baseline and PE, it can be concluded that the R2L ratios of area under the curve and peak value of the averaged contrast dilution curve are the most promising and reliable in assessing PE. It was also found that the efficacy of the two types of impedance contrasts were not significantly different in distinguishing PE from baseline in our model.

Vitamin D deficiency: What does it mean for chronic obstructive pulmonary disease (COPD)? a compherensive review for pulmonologists.

Science.gov (United States)

Kokturk, Nurdan; Baha, Ayse; Oh, Yeon-Mok; Young Ju, Jung; Jones, Paul W

2018-02-01

Vitamin D deficiency and Chronic Obstructive Pulmonary Disease (COPD) are both under-recognized health problems, world-wide. Although Vitamin D has long been known for calcemic effects it also has less known noncalcemic effects. Recent data have shown that Vitamin D deficiency is highly prevalent in patients with COPD and correlates with forced expiratory volume in one second (FEV 1 ) and FEV 1 decline. The objective of this work was to review the current literature on vitamin D deficiency in relation with COPD. A literature search, using the words "vitamin D" and "COPD", was undertaken in Pubmed database. The noncalcemic effects of vitamin D relating with COPD may be summarised as increasing antimicrobial peptide production, regulation of inflammatory response and airway remodelling. Vitamin D inhibits the production of several proinflammatory cytokines and leads to suppression Th1 and Th17 responses which may be involved in the pathogenesis of COPD. Vitamin D insufficiency may also contribute to chronic respiratory infections and airway colonization so returning vitamin D concentrations to an optimal range in patients with COPD might reduce bacterial load and concomitant exacerbations.Vitamin D is also important for COPD-related comorbodities such as osteoporosis, muscle weakness and cardiovascular diseases. Data about the effect of Vitamin D supplementation on those comorbidities in relation with COPD are been scarce. Improving the blood level of Vitamin D into the desired range may have a beneficial effect bones and muscles, but more studies are needed to test to test that hypothesis. © 2017 John Wiley & Sons Ltd.

Improving adherence to alpha-1 antitrypsin deficiency screening guidelines using the pulmonary function laboratory

Directory of Open Access Journals (Sweden)

Luna Diaz LV

2017-07-01

Full Text Available Landy V Luna Diaz,1 Isabella Iupe,1 Bruno Zavala,1 Kira C Balestrini,1 Andrea Guerrero,1 Gregory Holt,1,2 Rafael Calderon-Candelario,1,2 Mehdi Mirsaeidi,1,2 Michael Campos1,21Miami Veterans Administration Medical Center, Miami, FL, 2Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Miami School of Medicine, Miami, FL, USAAlpha-1 antitrypsin deficiency (AATD is the only well-recognized genetic disorder associated with an increased risk of emphysema and COPD.1 Identifying AATD allows genetic counseling and the chance to offer specific augmentation therapy to slow emphysema progression. Despite specific recommendations from the World Health Organization, American Thoracic Society and European Respiratory Society to screen all patients with COPD and other at-risk conditions,2–4 testing rates are low (<15%.5We conducted a project to improve AATD screening at the Miami VA Medical Center using the pulmonary function test (PFT laboratory. We instructed the PFT personnel to perform reflex testing on all patients with pre-bronchodilator airflow obstruction (forced expiratory volume in 1 second/forced vital capacity <70% and then evaluated if the screening was appropriate according to guidelines. Trained PFT personnel explained AATD disease to patients and provided them with an informational brochure. After obtaining verbal consent, AATD screening was performed using dried blood spot kits provided by the Alpha-1 Foundation as part of the Florida Screening Program (noncommercial.6 The PFT lab director was the responsible physician of record, in charge of discussing positive results to patients and documenting results in the electronic medical record. The Miami Veterans Affairs Medical Center Institutional Review Board approved the protocol as a quality improvement project.

Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

Science.gov (United States)

Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

2017-04-01

To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Enhancing psychological capital and personal growth initiative: working on strengths or deficiencies.

Science.gov (United States)

Meyers, Maria Christina; van Woerkom, Marianne; de Reuver, Renee S M; Bakk, Zsuzsa; Oberski, Daniel L

2015-01-01

Personal growth initiative (PGI), defined as being proactive about one's personal development, is critical to graduate students' academic success. Prior research has shown that students' PGI can be enhanced through interventions that focus on stimulating developmental activities. Within this study, we aimed to investigate whether an intervention that stimulates development in the area of one's personal strengths (strengths intervention) has more beneficial effects on students' PGI than an intervention that stimulates development in the area of individual deficiencies (deficiency intervention). We conducted 2 longitudinal field experiments to investigate the effects of the 2 interventions on students' PGI (Experiment 1) and the potential mediating role of psychological capital (PsyCap) in this regard (Experiment 2). In Experiment 1, 105 (N = 105) university students participated in either a strengths intervention or a deficiency intervention. Results indicated that the strengths intervention increased the students' PGI in the short but not in the long term, whereas the deficiency intervention did not affect PGI. Ninety students (N = 90) participated in Experiment 2, in which we slightly refined both interventions by putting a stronger emphasis on the ongoing development of strengths (strengths intervention) or correction of deficiencies (deficiency intervention) by adding posttraining assignments. Results suggested that participating in both interventions led to increases in PGI over a 3-month period, but that these increases were bigger for the strengths intervention group. Furthermore, the relationship between the strengths intervention and PGI was mediated by hope as one component of PsyCap. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn

Science.gov (United States)

Lakshminrusimha, Satyan; Porta, Nicolas F. M.; Farrow, Kathryn N.; Chen, Bernadette; Gugino, Sylvia F.; Kumar, Vasanth H.; Russell, James A.; Steinhorn, Robin H.

2009-01-01

Prostacyclin is a pulmonary vasodilator and is produced by prostacyclin synthase and stimulates adenylate cyclase (AC) via the prostacyclin receptor (IP) to produce cAMP. Forskolin is a direct stimulant of AC. Phosphodiesterase 3 hydrolyzes cAMP and is inhibited by milrinone. Objective To characterize the prostacyclin-AC-cAMP pathway in the ovine ductal ligation model of persistent pulmonary hypertension of the newborn (PPHN). Setting University-based laboratory animal facility. Subjects Lambs delivered to time-dated pregnant ewes. Interventions Fifth generation pulmonary arteries (PA) and lung parenchyma were isolated from control fetal lambs (n = 8) and fetal lambs with PPHN induced by antenatal ductal ligation (n = 9). We studied relaxation responses to various agonists (milrinone, forskolin, prostacyclin, and iloprost, a prostacyclin analog) that increase cAMP in PA after half-maximal constriction with norepinephrine and pretreatment with propranolol ± indo-methacin. Lung protein levels of prostacyclin synthase, IP, AC2, and phosphodiesterase 3A were analyzed by Western blot and cAMP by enzyme-linked immunoassay. Main Results Milrinone relaxed control and PPHN PA and pretreatment with indomethacin significantly impaired this response. Relaxation to milrinone, prostacyclin, and iloprost were significantly impaired in PA from PPHN lambs. Pretreatment with milrinone markedly enhanced relaxation to prostacyclin and iloprost in PPHN PA, similar to relaxation in control PA. Relaxation to forskolin was similar in control and PPHN PAs indicating normal AC activity. Protein levels of prostacyclin synthase and IP were decreased in PPHN lungs compared with control, but AC2, cAMP, and phosphodiesterase 3A remained unchanged. Conclusions Prostacyclin and iloprost are dilators of PAs from PPHN lambs and their effect is enhanced by milrinone. This combination therapy may be an effective strategy in the management of patients with PPHN. PMID:19057444

Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

Science.gov (United States)

Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

2015-12-01

Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

International Nuclear Information System (INIS)

Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

2016-01-01

Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

Vitamin d status in patients with chronic obstructive pulmonary disease who participate in pulmonary rehabilitation

DEFF Research Database (Denmark)

Ringbaek, Thomas; Martinez, Gerd; Durakovic, Amal

2011-01-01

PURPOSE: Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease; however, no study has evaluated the influence of vitamin D status on effects of pulmonary rehabilitation (PR). METHODS: We studied 311 patients, who participated in a 7-week outpatient PR. Vitamin D...... higher body mass index and fat-free mass index, had worse quality of life score, tended to have lower percent predicted value for forced expiratory volume in the first second of expiration, and more frequently were current smokers. They had a 3-time higher risk of dropout from the PR program (P = .003...

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

Science.gov (United States)

Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Comparative diagnostic value of pulmonary perfusion and ventilation scintigraphy and angiopneumography in pulmonary embolism

International Nuclear Information System (INIS)

Peltier, P.; Cesbron, J.P.; Dupas, B.; Crochet, D.; Delhumeau, J.

1984-01-01

Fourty-six patients suspected clinically of having a pulmonary embolism (PE) were investigated by angiopneumography (AGP) and perfusion (99m-Tc aggregates) and ventilation (99m-Tc colloid) scintigraohy (SPV Tc). Findings were assessed under blind conditions. A positive diagnosis of pulmonary embolism was made in 19 patients. The SPV Tc was considered as positive if perfusional deficiencies were greater than ventilatory defects, and this was evaluated as such in 23 cases (19 true and 4 false positives). False negatives were not observed. The 4 false positive results corresponded to scintigraphic anomalies suggestive of pulmonary emboli subsegmental in size; true positives were either subsegmental (8), segmental (6) or lobar (5). Sensitivity of the SPV Tc was therefore 100 %; its specificity, all results considered was 76 %, but was 100 % if only images of lobar or segmental lesions are considered [fr

Performance of the Androgen Deficiency in Aging Male ...

African Journals Online (AJOL)

failure, chronic liver disease, chronic renal failure, tuberculosis, chronic obstructive pulmonary diseases, acquired immunodeficiency syndrome and malignancy. Relevant socio- demographic and diabetes-related information were documented. Clinical evaluation of androgen deficiency. Participants completed the original ...

Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice

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Esther K. Wolthuis

2012-01-01

Full Text Available Preventing tissue-factor-(TF- mediated systemic coagulopathy improves outcome in models of sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate ventilator-induced lung injury (VILI. We investigated the effect of relative TF deficiency on pulmonary coagulopathy and inflammation in a murine model of VILI. Heterozygous TF knockout (TF+/− mice and their wild-type (TF+/+ littermates were sedated (controls or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours. Mechanical ventilation resulted in pulmonary coagulopathy and inflammation, with more injury after mechanical ventilation with higher tidal volumes. Compared with TF+/+ mice, TF+/− mice demonstrated significantly lower pulmonary thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in lung wet-to-dry ratio, BALF total protein levels, neutrophil influx, and lung histopathology scores between TF+/− and TF+/+ mice. Notably, pulmonary levels of cytokines were significantly higher in TF+/− as compared to TF+/+ mice. Systemic levels of cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.

Oxygen-enhanced MRI vs. quantitatively assessed thin-section CT: Pulmonary functional loss assessment and clinical stage classification of asthmatics

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Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Koyama, Hisanobu [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Matsumoto, Keiko [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Department of Radiology, University of Yamanashi, 1100, Shimogatou, Chuo, Yamanashi, 409-3898 (Japan); Onishi, Yumiko [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Nogami, Munenobu [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan); Division of Image-Based Medicine, Institute of Biomedical Research and Innovation, 2-2 Minatojima Minamimachi Chuo-ku, Kobe, Hyogo, 650-0047 (Japan); Takenaka, Daisuke; Matsumoto, Sumiaki; Sugimura, Kazuro [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017 (Japan)

2011-01-15

Purpose: The purpose of this study was to prospectively compare the efficacy of oxygen-enhanced MR imaging (O{sub 2}-enhanced MRI) and CT for pulmonary functional loss assessment and clinical stage classification of asthmatics. Materials and methods: O{sub 2}-enhanced MRI, CT and %FEV{sub 1} measurement were used 34 consecutive asthmatics classified into four stages ('Mild Intermittent [n = 7]', 'Mild Persistent [n = 8], 'Moderate Persistent [n = 14]' and 'Severe Persistent [n = 5]'). Relative enhancement ratio maps for every subject were generated, and determine mean relative enhancement ratios (MRERs). Mean lung density (MLD) and the airway wall area (WA) corrected by body surface area (WA/BSA) were also measured on CT. To compare the efficacy of the two methods for pulmonary functional loss assessment, all indexes were correlated with %FEV{sub 1}. To determine the efficacy of the two methods for clinical stage classification, all parameters for the four clinical stages were statistically compared. Results: %FEV{sub 1} showed fair or moderate correlation with all parameters (0.15 {<=} r{sup 2} {<=} 0.30, p < 0.05). WA, WA/BSA and MRER of the 'Severe Persistent' group were significantly larger than those of 'Mild Intermittent' and 'Mild Persistent' groups (p < 0.05), and MRER of the 'Moderate Persistent' group significantly lower than that of the 'Mild Intermittent' group (p < 0.05). Conclusion: O{sub 2}-enhanced MRI is as effective as CT for pulmonary functional loss assessment and clinical stage classification of asthmatics.

Primed infusion with delayed equilibrium of Gd.DTPA for enhanced imaging of small pulmonary metastases.

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Kalber, Tammy L; Campbell-Washburn, Adrienne E; Siow, Bernard M; Sage, Elizabeth; Price, Anthony N; Ordidge, Katherine L; Walker-Samuel, Simon; Janes, Sam M; Lythgoe, Mark F

2013-01-01

To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung. A primed infusion with a delay before equilibrium (eqMRI) of the Gd(III) chelator Gd.DTPA, via the intraperitoneal route, was used to evaluate gadolinium tumor enhancement as a function of a bolus injection, which is applied routinely in the clinic, compared to gadolinium maintained at equilibrium. A double gated (respiration and cardiac) spin-echo sequence at 9.4T was used to evaluate whole lungs pre contrast and then at 15 (representative of bolus enhancement), 25 and 35 minutes (representative of eqMRI). This was carried out in two lung metastasis models representative of high and low tumor cell seeding. Lungs containing discrete tumor nodes where inflation fixed and taken for haematoxylin and eosin staining as well as CD34 staining for correlation to MRI. We demonstrate that sustained Gd enhancement, afforded by Gd equilibrium, increases the detection of pulmonary metastases compared to bolus enhancement and those tumors which enhance at equilibrium are sub-millimetre in size (<0.7 mm(2)) with a similar morphology to early bronchoalveolar cell carcinomas. As Gd-chelates are routinely used in the clinic for detecting tumors by MRI, this methodology is readily transferable to the clinic and advances MRI as a methodology for the detection of small pulmonary tumors.

Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

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Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

2009-01-01

Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

Pulmonary hypertension CT imaging

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Nedevska, A.

2013-01-01

Full text: The right heart catheterization is the gold standard in the diagnosis and determines the severity of pulmonary hypertension. The significant technical progress of noninvasive diagnostic imaging methods significantly improves the pixel density and spatial resolution in the study of cardiovascular structures, thus changes their role and place in the overall diagnostic plan. Learning points: What is the etiology, clinical manifestation and general pathophysiological disorders in pulmonary hypertension. What are the established diagnostic methods in the diagnosis and follow-up of patients with pulmonary hypertension. What is the recommended protocol for CT scanning for patients with clinically suspected or documented pulmonary hypertension. What are the important diagnostic findings in CT scan of a patient with pulmonary hypertension. Discussion: The prospect of instantaneous complex - anatomical and functional cardiopulmonary and vascular diagnostics seems extremely attractive. The contrast enhanced multislice computed (CT ) and magnetic resonance imaging are very suitable methods for imaging the structures of the right heart, with the possibility of obtaining multiple projections and three-dimensional imaging reconstructions . There are specific morphological features that, if carefully analyzed, provide diagnostic information. Thus, it is possible to avoid or at least reduce the frequency of use of invasive diagnostic cardiac catheterization in patients with pulmonary hypertension. Conclusion: This review focuses on the use of contrast-enhanced CT for comprehensive evaluation of patients with pulmonary hypertension and presents the observed characteristic changes in the chest, lung parenchyma , the structures of the right half of the heart and pulmonary vessels

Computed tomographic diagnosis of pulmonary artery aneurysm

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Maeno, Kouji; Kontani, Kazuhiro; Ito, Makoto; Sakurai, Noboru; Sawada, Taisei; Fukeda, Yasuhiko; Takata, Shigeo; Ikeda, Takayuki; Hattori, Nobu.

1986-01-01

Pulmonary artery aneurysms are rare lesions. Clagett et al reported that one aneurysm of the pulmonary artery may be found in approximately 14,000 necropsies. We have experienced a case of giant pulmonary artery aneurysm confirmed by computed tomography. A 38 year-old man with atrial septal defect admitted to Kanazawa City Hospital. He had been pointed out of a right hilar mass when he was 26 years old. His complaint was bloody sputum and cough. Pulmonary angiography was not useful for the definite diagnosis because of its mural thrombi. Enhanced computed tomography showed a giant pulmonary artery aneurysm with a mural thrombi in its cavity. This shows that enhanced computed tomography is very useful for the diagnosis of a pulmonary artery aneurysm with a mural thrombi in its cavity. (author)

Computed tomographic diagnosis of pulmonary artery aneurysm

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Maeno, Kouji; Kontani, Kazuhiro; Ito, Makoto; Sakurai, Noboru; Sawada, Taisei; Fukeda, Yasuhiko; Takata, Shigeo; Ikeda, Takayuki; Hattori, Nobu

1986-05-01

Pulmonary artery aneurysms are rare lesions. Clagett et al reported that one aneurysm of the pulmonary artery may be found in approximately 14,000 necropsies. We have experienced a case of giant pulmonary artery aneurysm confirmed by computed tomography. A 38 year-old man with atrial septal defect admitted to Kanazawa City Hospital. He had been pointed out of a right hilar mass when he was 26 years old. His complaint was bloody sputum and cough. Pulmonary angiography was not useful for the definite diagnosis because of its mural thrombi. Enhanced computed tomography showed a giant pulmonary artery aneurysm with a mural thrombi in its cavity. This shows that enhanced computed tomography is very useful for the diagnosis of a pulmonary artery aneurysm with a mural thrombi in its cavity.

Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer

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Gantt, R.; Parshad, R.; Price, F.M.; Sanford, K.K.

1986-01-01

Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility

Enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 deficient mice

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Zhang Zengli; Ding Xiaofei; Tong Jian; Li Bingyan

2011-01-01

To investigate whether impaired osteogenesis resulting from vitamin D deficiency can influence hematopoiesis recovery after radiation, the 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) gene knockout (KO) mice and wild type (WT) mice were subjected to different doses of gamma ray. The survival rates, peripheral blood cell counts and bone marrow cellularity were studied after irradiation (IR). The survival rates of the KO mice were significantly lower than that of WT mice after 6 or 8 Gy dose of radiation. The recovery of white blood cells in KO mice was significantly delayed compared with that in WT mice after radiation. The red blood cell number in WT mice was observed to increase more than that in KO mice at days 14 and 28 after radiation. The nadir platelet count in KO mice was nearly half of that in WT mice. Dramatically higher bone marrow cell numbers were found in WT mice compared with KO mice. Our findings demonstrate the enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 (1,25-(OH) 2 D 3 ) deficient mice. (author)

Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

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Min Yu

Full Text Available Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined.Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia.Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

Directory of Open Access Journals (Sweden)

Eileen M Bauer

Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: a pilot study

International Nuclear Information System (INIS)

Pienn, Michael; Balint, Zoltan; Kovacs, Gabor; Tscherner, Maria; Olschewski, Horst; Avian, Alexander; Johnson, Thorsten R.; Kullnig, Peter; Stollberger, Rudolf; Olschewski, Andrea

2014-01-01

In this pilot study we explored whether contrast-material bolus propagation time and speed in the pulmonary arteries (PAs) determined by dynamic contrast-enhanced computed tomography (DCE-CT) can distinguish between patients with and without pulmonary hypertension (PH). Twenty-three patients (18 with and 5 without PH) were examined with a DCE-CT sequence following their diagnostic or follow-up right-sided heart catheterisation (RHC). X-ray attenuation over time curves were recorded for regions of interest in the main, right and left PA and fitted with a spline fit. Contrast material bolus propagation speeds and time differences between the peak concentrations were compared with haemodynamic parameters from RHC. Bolus speed correlated (ρ = -0.55) with mean pulmonary arterial pressure (mPAP) and showed a good discriminative power between patients with and without PH (cut-off speed 317 mm/s; sensitivity 100 %/specificity 100 %). Additionally, time differences between peaks correlated with mPAP (ρ = 0.64 and 0.49 for right and left PA, respectively) and discrimination was achieved with sensitivity 100 %/specificity 100 % (cut-off time 0.15 s) and sensitivity 93 %/specificity 80 % (cut-off time 0.45 s), respectively. Bolus propagation speed and time differences between contrast material peaks in the PA can identify PH. This method could be used to confirm the indication for RHC in patients screened for pulmonary hypertension. (orig.)

Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: a pilot study

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Pienn, Michael; Balint, Zoltan [Ludwig Boltzmann Institute for Lung Vascular Research, Graz (Austria); Kovacs, Gabor; Tscherner, Maria; Olschewski, Horst [Ludwig Boltzmann Institute for Lung Vascular Research, Graz (Austria); Medical University of Graz, Division of Pulmonology, Department of Internal Medicine, Graz (Austria); Avian, Alexander [Ludwig Boltzmann Institute for Lung Vascular Research, Graz (Austria); Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Graz (Austria); Johnson, Thorsten R. [Ludwig Maximilians University, Department of Clinical Radiology, Munich (Germany); Kullnig, Peter [DiagnostikZentrum Graz, Graz (Austria); Stollberger, Rudolf [Graz University of Technology, Institute for Medical Engineering, Graz (Austria); Olschewski, Andrea [Ludwig Boltzmann Institute for Lung Vascular Research, Graz (Austria); Medical University of Graz, Experimental Anesthesiology, Department of Anesthesia and Intensive Care Medicine, Graz (Austria)

2014-03-15

In this pilot study we explored whether contrast-material bolus propagation time and speed in the pulmonary arteries (PAs) determined by dynamic contrast-enhanced computed tomography (DCE-CT) can distinguish between patients with and without pulmonary hypertension (PH). Twenty-three patients (18 with and 5 without PH) were examined with a DCE-CT sequence following their diagnostic or follow-up right-sided heart catheterisation (RHC). X-ray attenuation over time curves were recorded for regions of interest in the main, right and left PA and fitted with a spline fit. Contrast material bolus propagation speeds and time differences between the peak concentrations were compared with haemodynamic parameters from RHC. Bolus speed correlated (ρ = -0.55) with mean pulmonary arterial pressure (mPAP) and showed a good discriminative power between patients with and without PH (cut-off speed 317 mm/s; sensitivity 100 %/specificity 100 %). Additionally, time differences between peaks correlated with mPAP (ρ = 0.64 and 0.49 for right and left PA, respectively) and discrimination was achieved with sensitivity 100 %/specificity 100 % (cut-off time 0.15 s) and sensitivity 93 %/specificity 80 % (cut-off time 0.45 s), respectively. Bolus propagation speed and time differences between contrast material peaks in the PA can identify PH. This method could be used to confirm the indication for RHC in patients screened for pulmonary hypertension. (orig.)

Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

Science.gov (United States)

Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

2018-01-15

Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

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Johns, Christopher S.; Swift, Andrew J.; Hughes, Paul J.C. [University of Sheffield (United Kingdom); Ohno, Yoshiharu [Division of Functional and Diagnostic Imaging Research, Department of Radiology, KobeUniversity Graduate School of Medicine, Kobe, Hyogo (Japan); Schiebler, Mark [UW-Madison School of Medicine and Public Health, Madison, WI (United States); Wild, Jim M., E-mail: j.m.wild@sheffield.ac.uk [University of Sheffield (United Kingdom)

2017-01-15

Highlights: • This article represents an overview of the methodology and clinical applications of pulmonary MRA and perfusion imaging. • Both contrast enhanced and non-contrast enhanced metholodology for MRA and perfusion are covered. • The current clinical uses and future directions of MRA and MR perfusion are discussed. - Abstract: The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology.

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

International Nuclear Information System (INIS)

Johns, Christopher S.; Swift, Andrew J.; Hughes, Paul J.C.; Ohno, Yoshiharu; Schiebler, Mark; Wild, Jim M.

2017-01-01

Highlights: • This article represents an overview of the methodology and clinical applications of pulmonary MRA and perfusion imaging. • Both contrast enhanced and non-contrast enhanced metholodology for MRA and perfusion are covered. • The current clinical uses and future directions of MRA and MR perfusion are discussed. - Abstract: The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology.

Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

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Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

2016-10-15

Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

Bilateral meandering pulmonary veins

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Thupili, Chakradhar R.; Udayasankar, Unni [Pediatric Imaging, Imaging Institute Cleveland Clinic, Cleveland, OH (United States); Renapurkar, Rahul [Imaging Institute Cleveland Clinic, Thoracic Imaging, L10, Cleveland, OH (United States)

2015-06-15

Meandering pulmonary veins is a rare clinical entity that can be mistaken for more complex congenital syndromes such as hypogenetic lung syndrome. We report imaging findings in a rare incidentally detected case of bilateral meandering pulmonary veins. We briefly discuss the role of imaging in diagnosing this condition, with particular emphasis on contrast-enhanced CT. (orig.)

Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

Science.gov (United States)

Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

2016-01-01

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

DNA Damage and Pulmonary Hypertension

Science.gov (United States)

Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

2016-01-01

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

Three cases of pulmonary varix

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Takishima, Teruo; Sakuma, Hajime; Tajima, Tsunemi; Okimoto, Takao; Yamamoto, Keiichiro; Dohi, Yutaka (Saitama Medical School (Japan))

1982-06-01

Three cases of pulmonary varix associated with valvular heart disease were reported. Round shadows were clearer on first oblique or lateral films of chest x-ray in all 3 cases. On chest tomograms, the shadows were substantial and round-elliptical. RI angiography with sup(99m)Tc-RBC demonstrated these shadows in agreement with the site of influx of the pulmonary vein into the left atrium in Cases 1 and 3 and with the pulmonary vein slightly apart from the left atrium in Case 2. On CT scans in Cases 1 and 3, enhancement with a contrast medium visualized dilatation of the pulmonary vein close to, and in continuation with, the shadow of the left atrium. The diagnosis of pulmonary varix in agreement with the venous phase of pulmonary angiography was made for all 3 cases. Non-surgical examinations (especially CT scan) proved highly useful for the diagnosis of pulmonary varix.

Bilateral multiple pulmonary artery aneurysms associated with cavitary pulmonary tuberculosis: a case report.

Science.gov (United States)

Pallangyo, Pedro; Lyimo, Frederick; Bhalia, Smita; Makungu, Hilda; Nyangasa, Bashir; Lwakatare, Flora; Suranyi, Pal; Janabi, Mohamed

2017-07-19

Pulmonary artery aneurysms constitute 50%) of cases, however, pulmonary artery aneurysm is a rare sequelae of pulmonary tuberculosis reported in about 5% of patients with chronic cavitary tuberculosis on autopsy. The natural history of this potentially fatal condition remains poorly understood and guidelines for optimal management are controversial. A 24-year-old man, a nursing student of African descent, was referred to us from an up-country regional hospital with a 4-week history of recurrent episodes of breathlessness, awareness of heartbeats and coughing blood 3 weeks after completing a 6-month course of anti-tuberculosis drugs. A physical examination revealed conjuctival and palmar pallor but there were no stigmata of connective tissue disorders, systemic vasculitides or congenital heart disease. An examination of the cardiovascular system revealed accentuated second heart sound (S 2 ) with early diastolic (grade 1/6) and holosystolic (grade 2/6) murmurs at the pulmonic and tricuspid areas respectively. Blood tests showed iron deficiency anemia, prolonged bleeding time, and mild hyponatremia. A chest radiograph revealed bilateral ovoid-shaped perihilar opacities while a computed tomography scan showed bilateral multiple pulmonary artery pseudoaneurysms with surrounding hematoma together with adjacent cystic changes, consolidations, and tree-in-bud appearance. Our patient refused to undergo surgery and died of aneurismal rupture after 9 days of hospitalization. The presence of intractable hemoptysis among patients with tuberculosis even after completion of anti-tuberculosis course should raise an index of suspicion for pulmonary artery aneurysm. Furthermore, despite of its rarity, early recognition and timely surgical intervention of pulmonary artery aneurysm is crucial to reducing morbidity and preventing the attributed mortality.

The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis

Directory of Open Access Journals (Sweden)

Vin Tangpricha

2017-06-01

Full Text Available Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF. Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC study, a multi-center, double-blind, randomized, placebo-controlled trial, will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 h of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 s (FEV1, blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.

Evaluation of pulmonary artery flow in acute massive pulmonary thromboembolism with MRI

International Nuclear Information System (INIS)

Li Yongzhong; Li Kuncheng; Zhao Xigang; Zhao Hong

2004-01-01

Objective: To probe into the value of MR imaging in evaluating the pulmonary artery hemodynamics and pulmonary artery pressure in acute massive pulmonary embolism. Methods: MR studies were performed in 21 patients with acute massive pulmonary embolism (diagnosed by contrast enhanced MR pulmonary angiography) and 20 healthy volunteers. The pulmonary artery hemodynamic parameters, such as the diameters of main and right pulmonary artery, peak velocity, average velocity, flow volume, flow patterns, and ejection acceleration time in main pulmonary artery were measured. The findings in patients and volunteers were compared. The hemodynamic parameters in patients were correlated with mean pulmonary artery pressure acquired with right heart catheterization. Results: The diameters of main pulmonary artery (2.93 vs 2.52 cm) and right pulmonary artery (2.49 vs 1.92 cm) in patients and volunteers showed significant differences (t=3.55, P<0.01 and t=4.19, P<0.01, respectively); Peak velocity (85.29 vs 100.63 cm/s), average velocity (11.00 vs 17.12 cm/s), flow volume (89.15 vs 98.96 ml/s), and ejection acceleration time (105.09 vs 163.85 ms) in main pulmonary artery were significantly different between patients and volunteers (t values were 2.89, 6.37, 2.21, and 9.46, respectively; P values were 0.01, <0.01, 0.03, and <0.01, respectively). The peak velocity-time curve of main pulmonary artery acquired with velocity encoded cine of MR in patients demonstrated earlier and lower peak velocity as well as abnormal retrograde flow. In addition, linear correlations were seen between the mean pulmonary pressure and the diameter of main pulmonary artery (r=0.62, P=0.001), diameter of right pulmonary artery (r=0.63, P=0.001), and ejection acceleration time (r=-0.55, P=0.005). Conclusion: MR imaging is a promising technique not only for the detection of pulmonary thromboemboli but also for the evaluation of hemodynamic parameters in pulmonary hypertension. (author)

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

Science.gov (United States)

Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

2011-09-21

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Three cases of pulmonary varix

International Nuclear Information System (INIS)

Takishima, Teruo; Sakuma, Hajime; Tajima, Tsunemi; Okimoto, Takao; Yamamoto, Keiichiro; Dohi, Yutaka

1982-01-01

Three cases of pulmonary varix associated with valvular heart disease were reported. Round shadows were clearer on first oblique or lateral films of chest x-ray in all 3 cases. On chest tomograms, the shadows were substantial and round-elliptical. RI angiography with sup(99m)Tc-RBC demonstrated these shadows in agreement with the site of influx of the pulmonary vein into the left atrium in Cases 1 and 3 and with the pulmonary vein slightly apart from the left atrium in Case 2. On CT scans in Cases 1 and 3, enhancement with a contrast medium visualized dilatation of the pulmonary vein close to, and in continuation with, the shadow of the left atrium. The diagnosis of pulmonary varix in agreement with the venous phase of pulmonary angiography was made for all 3 cases. Non-surgical examinations (especially CT scan) proved highly useful for the diagnosis of pulmonary varix. (Chiba, N.)

Prevalence of renal artery stenosis in flash pulmonary oedema: determination using gadolinium-enhanced MRA.

LENUS (Irish Health Repository)

McMahon, Colm J

2012-02-01

PURPOSE: The primary purpose was to determine the prevalence of renal artery stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema (FPE), without identifiable cause using contrast-enhanced magnetic resonance angiography (CE-MRA) of renal arteries. A secondary goal was to correlate clinical parameters at presentation with the presence or absence of RAS. MATERIALS AND METHODS: Patients presenting with acute pulmonary oedema without identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was considered significant. Clinical parameters (blood pressure, serum creatinine, history of hypertension\\/hyperlipidaemia) were compared in patients with and without RAS using an unpaired t-test. Results expressed; mean (+\\/-SD). RESULTS: 20 patients (4 male, 16 female, age 78.5+\\/-11 years) underwent CE-MRA. 9 patients (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP was higher in patients with RAS (192+\\/-38 mm Hg) than those without (134+\\/-30 mm Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+\\/-23 mm Hg) than those without (76+\\/-17 mm Hg) (p<.01). All patients with RAS and 6\\/11(55%) patients without RAS had a history of hypertension. No significant difference in creatinine or hyperlipidaemia history was observed. CONCLUSION: The prevalence of RAS in patients presenting with FPE is 45%. The diagnosis should be considered in patients presenting with unexplained acute pulmonary oedema, particularly if hypertensive at presentation.

Pathophysiology and treatment of pulmonary hypertension in sickle cell disease

Science.gov (United States)

Castro, Oswaldo L.; Machado, Roberto F.

2016-01-01

Pulmonary hypertension affects ∼10% of adult patients with sickle cell disease (SCD), particularly those with the homozygous genotype. An increase in pulmonary artery systolic pressure, estimated noninvasively by echocardiography, helps identify SCD patients at risk for pulmonary hypertension, but definitive diagnosis requires right-heart catheterization. About half of SCD-related pulmonary hypertension patients have precapillary pulmonary hypertension with potential etiologies of (1) a nitric oxide deficiency state and vasculopathy consequent to intravascular hemolysis, (2) chronic pulmonary thromboembolism, or (3) upregulated hypoxic responses secondary to anemia, low O2 saturation, and microvascular obstruction. The remainder have postcapillary pulmonary hypertension secondary to left ventricular dysfunction. Although the pulmonary artery pressure in SCD patients with pulmonary hypertension is only moderately elevated, they have a markedly higher risk of death than patients without pulmonary hypertension. Guidelines for diagnosis and management of SCD-related pulmonary hypertension were published recently by the American Thoracic Society. Management of adults with sickle-related pulmonary hypertension is based on anticoagulation for those with thromboembolism; oxygen therapy for those with low oxygen saturation; treatment of left ventricular failure in those with postcapillary pulmonary hypertension; and hydroxyurea or transfusions to raise the hemoglobin concentration, reduce hemolysis, and prevent vaso-occlusive events that cause additional increases in pulmonary pressure. Randomized trials have not identified drugs to lower pulmonary pressure in SCD patients with precapillary pulmonary hypertension. Patients with hemodynamics of pulmonary arterial hypertension should be referred to specialized centers and considered for treatments known to be effective in other forms of pulmonary arterial hypertension. There have been reports that some of these treatments

Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

DEFF Research Database (Denmark)

Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U

2012-01-01

Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese....... However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood...... pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight...

Pulmonary embolism in pregnancy: comparison of pulmonary CT angiography and lung scintigraphy.

LENUS (Irish Health Repository)

Ridge, Carole A

2012-02-01

OBJECTIVE: The purpose of this study was to retrospectively compare the diagnostic adequacy of lung scintigraphy with that of pulmonary CT angiography (CTA) in the care of pregnant patients with suspected pulmonary embolism. MATERIALS AND METHODS: Patient characteristics, radiology report content, additional imaging performed, final diagnosis, and diagnostic adequacy were recorded for pregnant patients consecutively referred for lung scintigraphy or pulmonary CTA according to physician preference. Measurements of pulmonary arterial enhancement were performed on all pulmonary CTA images of pregnant patients. Lung scintigraphy and pulmonary CTA studies deemed inadequate for diagnosis at the time of image acquisition were further assessed, and the cause of diagnostic inadequacy was determined. The relative contribution of the inferior vena cava to the right side of the heart was measured on nondiagnostic CTA images and compared with that on CTA images of age-matched nonpregnant women, who were the controls. RESULTS: Twenty-eight pulmonary CTA examinations were performed on 25 pregnant patients, and 25 lung scintigraphic studies were performed on 25 pregnant patients. Lung scintigraphy was more frequently adequate for diagnosis than was pulmonary CTA (4% vs 35.7%) (p = 0.0058). Pulmonary CTA had a higher diagnostic inadequacy rate among pregnant than nonpregnant women (35.7% vs 2.1%) (p < 0.001). Transient interruption of contrast material by unopacified blood from the inferior vena cava was identified in eight of 10 nondiagnostic pulmonary CTA studies. CONCLUSION: We found that lung scintigraphy was more reliable than pulmonary CTA in pregnant patients. Transient interruption of contrast material by unopacified blood from the inferior vena cava is a common finding at pulmonary CTA of pregnant patients.

Association of vitamin d deficiency with tuberculosis in adult patients reporting to a tertiary care hospital of rawalpindi

International Nuclear Information System (INIS)

Mashhadi, S.F.; Rahman, M.U.; Hashim, R.; Azam, N.

2014-01-01

To compare the mean vitamin Dlevels in pulmonary tuberculosis patients and healthy controls and to find out the frequency and association of vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Pulmonology department, Military Hospital Rawalpindi from Jan 2013 to Dec 2013. Patients and Methods:Fifty two incident outdoor pulmonary tuberculosis patients were selected with 52 age and gender matched controls. Tuberculosis was diagnosed by the sputum examination through gene Xpert technique from National Institute of Health (NIH), Islamabad. Serum 25-hydroxvitamin D level 0.05). Conclusion: Significant vitamin D deficiency was seen in newly diagnosed TB patients. It was found that vitamin D deficiency is associated with tuberculosis, but its causal role has not been established. (author)

Synthesis of surface oxygen-deficient BiPO{sub 4} nanocubes with enhanced visible light induced photocatalytic activity

Energy Technology Data Exchange (ETDEWEB)

Shi, Bingtao; Yin, Haoyong; Li, Tao; Gong, Jianying; Lv, Shumei; Nie, Qiulin, E-mail: yhy@hdu.edu.cn [College of Materials & Environmental Engineering, Hangzhou Dianzi University, Hangzhou (China)

2017-05-15

The visible light driven BiPO{sub 4} nanocubes with sufficient surface oxygen deficiency were fabricated by a hydrothermal process and subsequently ultrasonic assistant Fe reduction process. The products were characterized by XRD, DRS, XPS, SEM and TEM which showed that the BiPO{sub 4} had cuboid-like shape with a smooth surface and clear edges and the oxygen vacancies were successfully introduced on the surface of the BiPO{sub 4} nanocubes. The as prepared oxygen-deficient BiPO{sub 4} nanocubes showed greatly enhanced visible light induced photocatalytic activity in degradation of Rhodamine B. The enhanced photocatalytic performance and expanded visible light response of BiPO{sub 4} may be due to the introduction of surface oxygen vacancies which can generate the oxygen vacancies mid-gap states lower to the conduction band of BiPO{sub 4}. (author)

Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism : a prospective study

NARCIS (Netherlands)

Oudkerk, M; van Beek, EJR; Wielopolski, P; van Ooijen, PMA; Brouwers-Kuyper, EMJ; Bongaerts, AHH; Berghout, A

2002-01-01

Background Diagnostic strategies for pulmonary embolism are complex and consist of non-invasive diagnostic tests done to avoid conventional pulmonary angiography as much as possible. We aimed to assess the diagnostic accuracy of magnetic resonance angiography (MRA) for the diagnosis of pulmonary

Successful treatment of Rhodococcus equi pulmonary infection in a renal transplant recipient.

OpenAIRE

Marsh, H. P.; Bowler, I. C.; Watson, C. J.

2000-01-01

The rhodococcus is a mycobacterium-like organism which is normally a pathogen in foals. It usually spreads by direct contact or by aerosol from horse faeces and causes pyogranulomatous pulmonary infections. Occasionally, it acts opportunistically to infect immuno-compromised human hosts, most commonly those with the acquired immune deficiency syndrome (AIDS). Here we report a pulmonary infection by Rhodococcus equi in a renal transplant recipient who was successfully treated. The literature o...

Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension.

Directory of Open Access Journals (Sweden)

Benoît Gore

Full Text Available Mutations affecting transforming growth factor-beta (TGF-β superfamily receptors, activin receptor-like kinase (ALK-1, and endoglin (ENG occur in patients with pulmonary arterial hypertension (PAH. To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs and pulmonary endothelial cells (PECs from 14 patients with idiopathic PAH (iPAH and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV systolic pressure (RVSP, RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/- and wild-type (Eng+/+ mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.

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

Energy Technology Data Exchange (ETDEWEB)

Nagel, Sebastian Niko, E-mail: sebastian.nagel@charite.de [Klinik und Hochschulambulanz für Radiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Kim, Damon, E-mail: damon.kim@charite.de [Klinik und Hochschulambulanz für Radiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Institut für Röntgendiagnostik, HELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin (Germany); Penzkofer, Tobias, E-mail: tobias.penzkofer@charite.de [Klinik und Hochschulambulanz für Radiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Steffen, Ingo G., E-mail: ingo.steffen@charite.de [Klinik und Hochschulambulanz für Radiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); Wyschkon, Sebastian, E-mail: sebastian.wyschkon@charite.de [Klinik und Hochschulambulanz für Radiologie, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin (Germany); and others

2017-04-15

Objective: To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions. Materials and methods: 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 ((SI{sub Lesion} − SI{sub Muscle})/(SI{sub Fat} − SI{sub Muscle})*100) were calculated from the T2-weighted images using the mean SI (T2-NICQ{sub mean}) or the 90th percentile of SI (T2-NICQ{sub 90th}) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Q{sub mean}: SI{sub Lesion}/SI{sub Muscle}). Results: Infectious pulmonary lesions showed a higher T2-NICQ{sub mean} (40.1 [14.6–56.0] vs. 20.9 [2.4–30.1], p < 0.05) and T2-NICQ{sub 90th} (74.3 [43.8–91.6] vs. 38.5 [15.8–48.1], p < 0.01) than malignant lesions. T1-Q{sub mean} 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-NICQ{sub 90th} was lower when anti-infectious treatment was administered >24 h 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-NICQ{sub mean} (YI = 0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ{sub 90th} (YI = 0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ{sub 90th} and T1-Q{sub mean} increased diagnostic performance (YI = 0.72, 0.77 sensitivity, 0.95 specificity). Conclusion: Considering each quotient alone, T2-NICQ{sub 90th} showed the best diagnostic performance and

Salmeterol enhances pulmonary fibrinolysis in healthy volunteers

NARCIS (Netherlands)

Maris, Nico A.; de Vos, Alex F.; Bresser, Paul; van der Zee, Jaring S.; Jansen, Henk M.; Levi, Marcel; van der Poll, Tom

2007-01-01

OBJECTIVE: Various lung diseases are associated with local activation of coagulation and concurrent inhibition of fibrinolysis. Although salmeterol, a beta2-adrenoceptor agonist with profound bronchodilatory properties, has been studied extensively, the effects of this compound on the pulmonary

Pulmonary functional MR imaging for COPD

International Nuclear Information System (INIS)

Ohno, Yoshiharu

2008-01-01

Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airflow limitation, cough, sputum production, and, at later stages, dyspnea. COPD is currently the fourth-leading cause of mortality and the twelfth-leading cause of disability, and by the year 2020 it is expected to be the third-leading cause of death and the fifth-leading cause of disability worldwide. The diagnosis of COPD largely relies on a history of exposure to noxious stimuli and abnormal lung function test results. Since the pathology of COPD varies and the molecular mechanisms are only slightly understood, the diagnosis and stage assessment of COPD have relied on the results of pulmonary function test. In addition, CT and nuclear medicine study are utilized for assessment of regional morphological and functional abnormalities. Recently, pulmonary functional MR imaging is suggested as a new technique for assessment of regional physiopathologic information in various pulmonary diseases including COPD, pulmonary thromboembolism, lung cancer and interstitial lung diseases. This review article covers the brief description of theory and clinical application of contrast-enhanced perfusion MR imaging; hyperpolarized noble gas MR imaging and oxygen-enhanced MR imaging in COPD subjects. We believe that further basic studies as well as clinical applications of this new technique will define the real significance of pulmonary functional MR imaging for the future of pulmonary functional imaging and its usefulness for diagnosis and patients' management in COPD. (author)

A pilot trial on pulmonary emphysema quantification and perfusion mapping in a single-step using contrast-enhanced dual-energy computed tomography.

Science.gov (United States)

Lee, Choong Wook; Seo, Joon Beom; Lee, Youngjoo; Chae, Eun Jin; Kim, Namkug; Lee, Hyun Joo; Hwang, Hye Jeon; Lim, Chae-Hun

2012-01-01

To know whether contrast-enhanced dual-energy computed tomography angiography (DECTA) can be used for simultaneous assessment of emphysema quantification and regional perfusion evaluation. We assessed 27 patients who had pulmonary emphysema and no pulmonary embolism on visual assessment of CT images, among 584 consecutive patients who underwent DECTA for the evaluation of pulmonary embolism. Virtual noncontrast (VNC) images were generated by modifying the "Liver VNC" application in a dedicated workstation. Using in-house software, the low-attenuation area below 950HU (LAA950), the 15th percentile attenuation (15pctlVNC) and the mean lung attenuation (MeanVNC) were calculated. The "Lung PBV" application was used to assess perfusion, and the low-iodine area below 5HU (LIA5), the 15th percentile iodine (15pctlIodine), and the mean iodine value (MeanIodine) were calculated from iodine map images. The correlation between VNC parameters and pulmonary function test data (available in 22 patients) and the correlation between VNC and iodine map parameters (all included 27 patients) were assessed. Color-coded map of VNC image were compared with iodine map images for the evaluation of regional heterogeneity. We observed moderate correlations between LAA950 and predicted %FEV1 (rs = -0.47, P VNC images. We observed moderate correlations between quantitative parameters on VNC images and pulmonary function test data, and also observed moderate correlations between the severity of parenchymal destruction, as determined from VNC images, and perfusion status, as determined from iodine maps. Therefore, the contrast-enhanced DECTA can be used for the emphysema quantification and regional perfusion evaluation by using the VNC images and iodine map, simultaneously.

Emphysema and bronchiectasis secondary to alpha-1 antitrypsin deficiency

International Nuclear Information System (INIS)

Fahim, A.; Hart, S.P.; Wilmot, R.

2013-01-01

A 47-year-old Caucasian male presented to the chest clinic with a 4-week history of exertional dyspnea. A chest radiograph showed mild hyperinflation without any focal pathology and spirometry showed a mild obstructive defect. In view of symptoms being disproportionate to spirometric and radiologic abnormalities, a thoracic CT scan was obtained. It revealed that there was evidence of bronchiectasis and mild emphysema in basal distribution. Subsequently, he was confirmed to have severe 1-Antitrypsin deficiency. This case illustrates the importance of considering 1-Antitrypsin deficiency in patients with combination of emphysema and bronchiectasis in a basal distribution. Although basal emphysema is well recognized pulmonary manifestation of 1-Antitrypsin deficiency, it is extremely unusual to have bronchiectasis with very mild degree of emphysema. (author)

ASSOCIATION OF VITAMIN D DEFICIENCY WITH TUBERCULOSIS IN ADULT PATIENTS REPORTING TO A TERTIARY CARE HOSPITAL OF RAWALPINDI

Directory of Open Access Journals (Sweden)

Syed Fawad Mashhadi

2014-09-01

Full Text Available Objectives: To compare the mean vitamin D levels in pulmonary tuberculosis patients and healthy controls and to find out the frequency and association of vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Pulmonology department, Military Hospital Rawalpindi from Jan 2013 to Dec 2013. Patients and Methods: Fifty two incident outdoor pulmonary tuberculosis patients were selected with 52 age and gender matched controls. Tuberculosis was diagnosed by the sputum examination through gene Xpert technique from National Institute of Health (NIH, Islamabad. Serum 25-hydroxvitamin D level 0.05. Conclusion: Significant vitamin D deficiency was seen in newly diagnosed TB patients. It was found that vitamin D deficiency is associated with tuberculosis, but its causal role has not been established.

MR-based assessment of pulmonary ventilation-perfusion in animal models

International Nuclear Information System (INIS)

Yang Jian; Wan Mingxi; Guo Youmin

2003-01-01

Objective: To show the feasibility and value in the diagnosis of airway obstruction and pulmonary embolism with MR oxygen-enhanced ventilation combined with pulmonary perfusion imaging. Methods: Eight canines were implemented for peripheral pulmonary embolism by intravenous injection of gelfoam granules at pulmonary segmental arterial level, and five of them were formed airway obstruction models by inserting self-made balloon catheter at second-bronchia. The oxygen-enhanced MR ventilation imaging was introduced by subtracting the images of pre- and post- inhaled pure oxygen. The MR pulmonary perfusion imaging was achieved by the first-pass contrast agent method. Moreover, the manifestation of MR ventilation and perfusion imaging was observed and contradistinguished with that of general pathologic anatomy, ventilation-perfusion scintigraphy, and pulmonary angiography. Results: The manifestations of airway obstruction regions in MR ventilation and perfusion imaging were matched, but those of pulmonary embolism regions were dismatched. The defect range of airway obstruction in MR ventilation image was smaller than that in ventilation scintigraphy. The abnormal perfusion regions of pulmonary embolism were divided into defect regions and reduce regions based on the time courses of signal intensity changes. The sensitivity and specificity of diagnosis on pulmonary embolism by MR ventilation combined with perfusion technique were 75.0% and 98.1%. The diagnostic results were in good coherence with ventilation-perfusion scintigraphy and pulmonary angiography (K=0.743, 0.899). Conclusion: The MR oxygen-enhanced ventilation combined with pulmonary perfusion imaging can be used to diagnose the airway and vascular abnormity in lung. This technique resembles the ventilation-perfusion scintigraphy. It can provide quantitative functional information and better spatial and temporal resolution, and possesses the value of clinical application

Pulmonary circulation

International Nuclear Information System (INIS)

Bongartz, G.; Boos, M.; Scheffler, K.; Steinbrich, W.

1998-01-01

Evaluation of the pulmonary vasculature is mainly indicated in patients with suspected pulmonary thromboembolism. The routine procedure so far is ventilation-perfusion scintigraphy alone or in combination with diagnostic assessment of the legs to rule out deep venous thrombosis. The results are still not reliable for the majority of patients. In the case of equivocal diagnosis, invasive conventional angiography is considered the gold standard. With steady improvements in tomographic imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), non-invasive alternatives to the routine diagnostic work-up are given. Helical CT and CTA techniques are already in clinical use and estimated to sufficiently serve the demands for detection/exclusion of pulmonary thromboembolism. The disadvantages mainly concern peripheral disease and reconstruction artifacts. MRI and MR angiography have been implemented in the diagnosis of pulmonary vascular disease since the introduction of contrast-enhanced MRA. In breath-hold techniques, the entire lung vascularization can be delineated and thromboemboli can be detected. The clinical experience in this field is limited, but MRI has the potential to demonstrate its superiority over CT due to its improved delineation of the vascular periphery and the more comprehensive three-dimensional reconstruction. (orig.)

Pulmonary spheral tuberculosis: features and clinical significance of spiral dynamic CT

International Nuclear Information System (INIS)

Xie Ruming; Ma Daqing; Li Tieyi; Chen Yi; Lu Fudong; Zhou Xinhua

2001-01-01

Objective: To assess the features and clinical significance of spiral dynamic CT in patients with pulmonary spheral tuberculosis. Methods: The 54 foci in 42 patients with pulmonary spheral tuberculosis were studied. Thin-sections at 2 mm thickness and 2 mm interval through the nodular center were obtained before and after administration of contrast material. Results: In 54 pulmonary spheral tuberculosis, maximum enhanced CT value in 51 (94.4%, 51/54) foci was less than 20 HU, and more than 20 HU in the other 3(5.6%, 3/54) foci. 27(50.0%, 27/54) foci showed no any enhancement, 24, (44%, 24/54) foci showed capsular enhancement, 1(1.9%, 1/54) focus showed peripheral enhancement and 2(3.7%, 2/54) foci showed extensive enhancement. The accuracy of the correct diagnosis was 25.9% in terms of plain CT and 94.4% in terms of enhanced CT scanning. The difference was significant (x 2 = 50.1, P < 0.05). The curative effect of extensive enhanced foci and peripheral enhanced foci was optimal, capsular enhanced foci was second, and non-enhanced foci was barely satisfactory. Conclusion: Spiral dynamic CT technique may improve the accuracy of diagnosing pulmonary spheral tuberculosis. No enhancement and/or capsular enhancement were suggestive of tuberculosis. The enhancing character of foci might contribute to assess the curative effect of anti-tuberculosis

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.

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Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J

2015-01-23

Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

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Larson JL

2014-10-01

Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. Methods: In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR, health education with upper body resistance training (ED-UBR, or health education with gentle chair exercises (ED-Chair. Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Results: Differences were observed in light physical activity (LPA after 4 months of training, time by group interaction effect (P=0.045. The SE-UBR group increased time spent in

Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

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Hornberger, Troy A; McLoughlin, Thomas J; Leszczynski, Jori K; Armstrong, Dustin D; Jameson, Ruth R; Bowen, Phyllis E; Hwang, Eun-Sun; Hou, Honglin; Moustafa, Mohamed E; Carlson, Bradley A; Hatfield, Dolph L; Diamond, Alan M; Esser, Karyn A

2003-10-01

Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.

Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.

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Ohno, Yoshiharu; Fujisawa, Yasuko; Takenaka, Daisuke; Kaminaga, Shigeo; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2018-02-01

The objective of this study was to compare the capability of xenon-enhanced area-detector CT (ADCT) performed with a subtraction technique and coregistered 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity in smokers. Forty-six consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent prospective unenhanced and xenon-enhanced ADCT, 81m Kr-ventilation SPECT/CT, and pulmonary function tests. Disease severity was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based functional lung volume (FLV), the percentage of wall area to total airway area (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for each smoker. All indexes were correlated with percentage of forced expiratory volume in 1 second (%FEV 1 ) using step-wise regression analyses, and univariate and multivariate logistic regression analyses were performed. In addition, the diagnostic accuracy of the proposed model was compared with that of each radiologic index by means of McNemar analysis. Multivariate logistic regression showed that %FEV 1 was significantly affected (r = 0.77, r 2 = 0.59) by two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p < 0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression analyses indicated that all indexes significantly affected GOLD classification (p < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD classification (p < 0.0001). The diagnostic accuracy of the proposed model was significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA% (p = 0.008). Xenon-enhanced ADCT is more effective than 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity.

Quality of CT pulmonary angiography for suspected pulmonary embolus in pregnancy

International Nuclear Information System (INIS)

U-King-Im, Jean Marie; Freeman, Susan J.; Boylan, Teresa; Cheow, Heok K.

2008-01-01

The main objective of this study was to assess the quality of CT pulmonary angiography (CTPA) for suspected pulmonary embolus (PE) in the pregnant population. We retrospectively identified 40 consecutive pregnant patients who underwent CTPA from January 2005 to December 2006. Forty consecutive age-matched non-pregnant women were used as a control group. Studies were subjectively graded according to overall image quality by two readers in consensus, in randomised and blinded manner. Moreover, contrast enhancement of pulmonary arteries was subjectively and objectively evaluated. The proportion of sub-optimal studies was more than three times higher in the pregnant group (27.5%, n = 11) compared with the non-pregnant group (7.5%, n = 3; p = 0.015). Mean contrast enhancement was consistently higher in the non-pregnant group compared with pregnant group, both subjectively and objectively. The percentage of inadequately opacified vascular segments was more than two times higher in the pregnant group (28.7%, n = 264) than in the non-pregnant group (13.3%, n 122; p = 0.0001). The incidence of sub-optimal CTPA studies is higher in pregnancy when compared with an age-matched non-pregnant control group. In addition to radiation issues, this should also be considered when implementing diagnostic strategies for suspected PE in pregnancy. (orig.)

Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease.

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Larson, Janet L; Covey, Margaret K; Kapella, Mary C; Alex, Charles G; McAuley, Edward

2014-01-01

People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. IN THIS RANDOMIZED CONTROLLED TRIAL, SUBJECTS WERE ASSIGNED TO: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair). Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045). The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by -22.43±47.88 minutes/day and -25.73±51.76 minutes/day. Changes in LPA were not sustained at 12-month follow-up. There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance. Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair. The self-efficacy enhancing intervention produced a modest short-term increase in LPA. Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA.

Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.

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Yoshino, Satoshi; Satoh, Tetsurou; Yamada, Masanobu; Hashimoto, Koshi; Tomaru, Takuya; Katano-Toki, Akiko; Kakizaki, Satoru; Okada, Shuichi; Shimizu, Hiroyuki; Ozawa, Atsushi; Tuchiya, Takafumi; Ikota, Hayato; Nakazato, Yoichi; Mori, Munemasa; Matozaki, Takashi; Sasaki, Tsutomu; Kitamura, Tadahiro; Mori, Masatomo

2014-09-01

Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

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Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

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Jacobsen, E A; Doyle, A D; Colbert, D C; Zellner, K R; Protheroe, C A; LeSuer, W E; Lee, N A; Lee, J J

2015-09-01

Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

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Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

2015-10-01

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

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Rui-Xing Wang

2015-03-01

Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

MR imaging of the pulmonary vasculature - an update

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Pedersen, Mark R.; Fisher, Mark T. [University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City, Iowa (United States); Beek, Edwin J.R. van [University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City, Iowa (United States); University of Iowa Hospitals and Clinics, JPP 3895, Department of Radiology, Iowa City, Iowa (United States)

2006-06-15

Although the advent of multi-detector row computed tomography (CT) angiography has been at the heart of improving the diagnostic management of pulmonary vascular disease, MR technology has also moved forward. This review outlines the current state of affairs of MR techniques for the assessment of pulmonary vascular diseases such as pulmonary hypertension, pulmonary arteritis and arteriovenous malformations. It highlights the main areas of MR angiography and MR perfusion imaging and discusses novel methods, such as non-contrast enhanced direct thrombus imaging, and will discuss its merits in the context of other diagnostic modalities. (orig.)

Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer

International Nuclear Information System (INIS)

Einhorn, L.; Krause, M.; Hornback, N.; Furnas, B.

1976-01-01

In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy of the lung

The dilatation of main pulmonary artery and right ventricle observed by enhanced chest computed tomography predict poor outcome in inoperable chronic thromboembolic pulmonary hypertension.

Science.gov (United States)

Ema, Ryogo; Sugiura, Toshihiko; Kawata, Naoko; Tanabe, Nobuhiro; Kasai, Hajime; Nishimura, Rintaro; Jujo, Takayuki; Shigeta, Ayako; Sakao, Seiichiro; Tatsumi, Koichiro

2017-09-01

Dilatation of the pulmonary artery and right ventricle on chest computed tomography images is often observed in patients with pulmonary hypertension. The clinical significance of these image findings has not been defined in chronic thromboembolic pulmonary hypertension. We investigated whether the pulmonary arterial and right ventricle dilatation was associated with poor outcome in chronic thromboembolic pulmonary hypertension. This was a retrospective cohort investigation in 60 subjects with inoperable chronic thromboembolic pulmonary hypertension diagnosed consecutively between 1997 and 2010 at Chiba University Hospital. Digital scout multi-detector chest computed tomography images were obtained. The main pulmonary arterial to ascending aortic diameter ratio and the right ventricular to left ventricular diameter ratio were calculated. Main pulmonary arterial to ascending aortic diameter ratio ranged from 0.85 to 1.84, and right ventricular to left ventricular diameter ratio ranged from 0.71 to 2.88. During the observation period of 1284.5days (range, 21-4550days), 13 patients required hospitalization due to worsening; 6 of them died. Kaplan-Meier analysis showed significant differences in hospitalization between the patients with main pulmonary arterial to ascending aortic diameter ratio of ≥1.1 and pulmonary hypertension. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pulmonary embolism; Lungenarterienembolie

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Sudarski, Sonja; Henzler, Thomas [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Inst. fuer Klinische Radiologie und Nuklearmedizin

2016-09-15

Pulmonary embolism (PE) requires a quick diagnostic algorithm, as the untreated disease has a high mortality and morbidity. Crucial for the diagnostic assessment chosen is the initial clinical likelihood of PE and the individual risk profile of the patient. The overall goal is to diagnose or rule out PE as quickly and safely as possible or to initiate timely treatment if necessary. CT angiography of the pulmonary arteries (CTPA) with multi-slice CT scanner systems presents the actual diagnostic reference standard. With CTPA further important diagnoses can be made, like presence of right ventricular dysfunction. There are different scan and contrast application protocols that can be applied in order to gain diagnostic examinations with sufficient contrast material enhancement in the pulmonary arteries while avoiding all kinds of artifacts. This review article is meant to be a practical guide to examine patients with suspected PE according to the actual guidelines.

A novel SERPINA1 mutation causing serum alpha(1-antitrypsin deficiency.

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Darren N Saunders

Full Text Available Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor α(1-Antitrypsin (α(1AT. α(1AT deficiency is the major contributor to pulmonary emphysema and liver disease in persons of European ancestry, with a prevalence of 1 in 2500 in the USA. We present the discovery and characterization of a novel SERPINA1 mutant from an asymptomatic Middle Eastern male with circulating α(1AT deficiency. This 49 base pair deletion mutation (T379Δ, originally mistyped by IEF, causes a frame-shift replacement of the last sixteen α(1AT residues and adds an extra twenty-four residues. Functional analysis showed that the mutant protein is not secreted and prone to intracellular aggregation.

Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

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DD Marciniuk

2012-01-01

Full Text Available Alpha-1 antitrypsin (A1AT functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD. Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted attributable to emphysema and documented A1AT deficiency (level ≤11 μmol/L who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation because of benefits in computed tomography scan lung density and mortality.

A study of images of Projective Angles of pulmonary veins

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Wang Jue [Beijing Anzhen Hospital, Beijing (China); Zhaoqi, Zhang [Beijing Anzhen Hospital, Beijing (China)], E-mail: zhaoqi5000@vip.sohu.com; Yu Wei; Miao Cuilian; Yan Zixu; Zhao Yike [Beijing Anzhen Hospital, Beijing (China)

2009-09-15

Aims: In images of magnetic resonance and computed tomography (CT) there are visible angles between pulmonary veins and the coronary, transversal or sagittal section of body. In this study these angles are measured and defined as Projective Angles of pulmonary veins. Several possible influential factors and characters of distribution are studied and analyzed for a better understanding of this imaging anatomic character of pulmonary veins. And it could be the anatomic base of adjusting correctly the angle of the central X-ray of the angiography of pulmonary veins undergoing the catheter ablation of atrial fibrillation (AF). Method: Images of contrast enhanced magnetic resonance angiography (CEMRA) and contrast enhanced computer tomography (CECT) of the left atrium and pulmonary veins of 137 health objects and patients with atrial fibrillation (AF) are processed with the technique of post-processing, and Projective Angles to the coronary and transversal sections are measured and analyzed statistically. Result: Project Angles of pulmonary veins are one of real and steady imaging anatomic characteristics of pulmonary veins. The statistical distribution of variables is relatively concentrated, with a fairly good representation of average value. It is possible to improve the angle of the central X-ray according to the average value in the selective angiography of pulmonary veins undergoing the catheter ablation of AF.

Protein S is protective in pulmonary fibrosis.

Science.gov (United States)

Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

2016-08-01

Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

Deficiency of thioredoxin binding protein-2 (TBP-2 enhances TGF-β signaling and promotes epithelial to mesenchymal transition.

Directory of Open Access Journals (Sweden)

So Masaki

Full Text Available Transforming growth factor beta (TGF-β has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT of various cancer cells. TGF-β-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1 is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer.In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.

Use of sodium chromate Cr51 in diagnosing childhood idiopathic pulmonary hemosiderosis

International Nuclear Information System (INIS)

Kurzweil, P.R.; Miller, D.R.; Freeman, J.E.; Reiman, R.E.; Mayer, K.

1984-01-01

The diagnosis of idiopathic pulmonary hemosiderosis (IPH) may be elusive. A 6-year-old boy had microcytic hypochromic anemia and a hemolytic component. Hemosiderin-laden macrophages were not found in the gastric aspirate. He had no pulmonary signs or symptoms. Extensive hematologic and roentgenologic investigations failed to reveal the cause of the anemia. Quantitative serial scintigraphic scanning showed significant (35%) pulmonary sequestration of autologous erythrocytes labeled with sodium chromate Cr51. The half-life of the RBCs was moderately decreased (half-life, 15 days; normal, 25 to 35 days). An open-lung biopsy spece Cr51. The half-life of the RBCs was moderately decreased (half-life, 15 days; normal, 25 to 35 days). An open-lung biopsy specimen confirmed the diagnosis of IPH. A diagnosis of IPH should be considered when children have iron deficiency anemia and pulmonary signs or symptoms. Organ sequestration studies may be helpful in equivocal cases

Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

LENUS (Irish Health Repository)

Flanagan, Frances

2013-03-01

Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC.

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

International Nuclear Information System (INIS)

Boll, Daniel T.; Lewin, Jonathan S.; Young, Philip; Gilkeson, Robert C.; Siwik, Ernest S.

2005-01-01

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, nonembolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel centerlines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries. (orig.)

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

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Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.

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Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K

2017-11-01

IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.

Dynamic Gd-DTPA enhanced breath-hold 1.5 t MRI of normal lungs and patients with interstitial lung disease and pulmonary nodules: preliminary results

International Nuclear Information System (INIS)

Semelka, R.C.; Maycher, B.; Shoenut, J.P.; Kroeker, R.; Griffin, P.; Lertzman, M.

1992-01-01

A FLASH technique was used, which encompassed the entire thorax in the transverse plane, before and after dynamic intravenous injection of godalinium DTPA (Gd-DTPA) to study 7 patients with normal lungs, 12 patients with interstitial lung disease (ILD), and 11 patients with pulmonary nodules. Comparative CT studies were obtained within 2 weeks of the MRI study in the patients with lung disease. Quantitative signal intensity (SI) measurements were performed. Qualitative evaluation of lung parenchyma was determined in a prospective blinded fashion, and in the normal group comparison was made with the CT images. In normal patients, SI of lung parenchyma increased by 7.7±1.3%. On precontrast images, second-order pulmonary branchings were visible while post-contrast, fifth- to sixth-order branches were apparent. In patients with ILD, interstitial changes enhanced to a variable extent, increases in SI ranging from minimal (49.9%) to substantial (308.4%). Detection of pulmonary nodules improved following contrast injection. The minimum lesion size detectable decreased from 8 mm precontrast to 5 mm post-contrast. Percentage contrast enhancement was greater for malignant nodules (124.2±79.7%) than benign nodules (5.8±4.7%) (p<0.01). (orig.)

Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

Directory of Open Access Journals (Sweden)

Paula E Beaumont

Full Text Available Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung infection was utilised, demonstrating cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both infection and peptide exposure and was independent of native cathelicidin production. Furthermore, although cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of cathelicidins in pulmonary infection in vivo and highlight a key role for cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial therapeutics. Elucidating and utilising the modulatory properties of cathelicidins has the potential to inform the development of synthetic peptide analogues and novel therapeutic approaches based on enhancing innate host defence against infection with or without direct microbicidal targeting of pathogens.

Modeling the influence of vitamin D deficiency on cigarette smoke-induced emphysema.

Directory of Open Access Journals (Sweden)

Mardi A. Crane-Godreau

2013-06-01

Full Text Available Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16 week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS, control diet with cigarette smoke exposure (CD-CSE, vitamin D deficient diet breathing room air (VDD-NS or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE. At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD.

A case of intralobar pulmonary sequestration

International Nuclear Information System (INIS)

Misawa, Takuo; Hongo, Minoru; Okubo, Shinichi; Yamada, Hiroyoshi; Matsuoka, Ken; Soga, Naoko; Kono, Jun; Kusama, Shozo

1985-01-01

A 57-year-old female was admitted to our hospital, complaining of hemoptysis. On auscultation, moist rales were audible at the lower portion of left posterior chest. Plain chest roentgenogram showed a round shadow in the left lower lung field. Computed tomography with contrast enhancement revealed an abnormal structure which was contiguous to a strand structure. Dynamic scanning demonstrated opacification of the strand structure and that of the greater part of the abnormal structure during peak opacification of the descending aorta. A part of the abnormal structure was opacified during the same phase as the opacification of the right ventricle and pulmonary artery. A diagnosis of intralobar pulmonary sequestration associated with pulmonary arterio-venous malformation was confirmed by thoracic aortography and left pulmonary arteriography. The hemoptysis was found to be caused by chronic bronchitis. It was emphasized that dynamic computed tomography is very useful to diagnose intralobar pulmonary sequestration and to assess the presence of pulmonary arterio-venous malformation. In addition, it is of particular interest that this case cannot be assigned to any category of Pryce's classification although it resembles both type I and IV. (author)

Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension

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Froelich, Jens J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: jens.froelich@klinikum-hef.de; Koenig, Helmut [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: helmut.koenig@siemens.com; Knaak, Lennard [Department of Medicine, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: froehlic@staff.uni-marburg.de; Krass, Stefan [MeVis Research, Universitaetsallee 29, 28359 Bremen (Germany)], E-mail: krass@mevis.de; Klose, Klaus J. [Department of Radiology, Philipps-University Hospital, Baldingerstrasse, 35043 Marburg (Germany)], E-mail: klose@med.uni-marburg.de

2008-09-15

Objectives: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. Materials and methods: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3 mm; pitch 2; increment 2 mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. Results: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r = .85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p < .005), PA volumes also were significantly increased (p < .05) among the groups. Conclusions: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension.

Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension

International Nuclear Information System (INIS)

Froelich, Jens J.; Koenig, Helmut; Knaak, Lennard; Krass, Stefan; Klose, Klaus J.

2008-01-01

Objectives: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. Materials and methods: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3 mm; pitch 2; increment 2 mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. Results: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r = .85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p < .005), PA volumes also were significantly increased (p < .05) among the groups. Conclusions: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension

Absorption of plutonium in the iron-deficient rat

International Nuclear Information System (INIS)

Ragan, H.A.

1977-01-01

Iron deficiency did not enhance absorption of plutonium following intragastric gavage of rats. Absorption of plutonium citrate in both control and iron-deficient rats was about 0.03% of the administered dose

[MRI methods for pulmonary ventilation and perfusion imaging].

Science.gov (United States)

Sommer, G; Bauman, G

2016-02-01

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

MRI methods for pulmonary ventilation and perfusion imaging

International Nuclear Information System (INIS)

Sommer, G.; Bauman, G.

2016-01-01

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O 2 -enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies. (orig.) [de

Pulmonary Hypertension and Pulmonary Vasodilators.

Science.gov (United States)

Keller, Roberta L

2016-03-01

Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

Receptor for advanced glycation endproducts (RAGE maintains pulmonary structure and regulates the response to cigarette smoke.

Directory of Open Access Journals (Sweden)

Lisa Wolf

Full Text Available The receptor for advanced glycation endproducts (RAGE is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/- mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Labeling the pulmonary arterial tree in CT images for automatic quantification of pulmonary embolism

NARCIS (Netherlands)

Peters, R.J.M.; Marquering, H.A.; Dogan, H.; Hendriks, E.A.; De Roos, A.; Reiber, J.H.C.; Stoel, B.C.

2007-01-01

Contrast-enhanced CT Angiography has become an accepted diagnostic tool for detecting Pulmonary Embolism (PE). The CT obstruction index proposed by Qanadli, which is based on the number of obstructed arterial segments, enables the quantification of PE severity. Because the required manual

MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

Science.gov (United States)

Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

2016-03-29

Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

Iron Deficiency and Anemia Predict Mortality in Patients with Tuberculosis123

Science.gov (United States)

Isanaka, Sheila; Mugusi, Ferdinand; Urassa, Willy; Willett, Walter C.; Bosch, Ronald J.; Villamor, Eduardo; Spiegelman, Donna; Duggan, Christopher; Fawzi, Wafaie W.

2012-01-01

Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB. PMID:22190024

Pulmonary ventilation and perfusion imaging with dual-energy CT

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Thieme, Sven F. [Klinikum Grosshadern, Department of Clinical Radiology, Ludwig Maximilians University, Muenchen (Germany); Klinikum Grosshadern, Institut fuer Klinische Radiologie, LMU Muenchen, Muenchen (Germany); Hoegl, Sandra; Fisahn, Juergen; Irlbeck, Michael [Klinikum Grosshadern, Department of Anesthesiology, Ludwig Maximilians University, Muenchen (Germany); Nikolaou, Konstantin; Maxien, Daniel; Reiser, Maximilian F.; Becker, Christoph R.; Johnson, Thorsten R.C. [Klinikum Grosshadern, Department of Clinical Radiology, Ludwig Maximilians University, Muenchen (Germany)

2010-12-15

To evaluate the feasibility of dual-energy CT (DECT) ventilation imaging in combination with DE perfusion mapping for a comprehensive assessment of ventilation, perfusion, morphology and structure of the pulmonary parenchyma. Two dual-energy CT acquisitions for xenon-enhanced ventilation and iodine-enhanced perfusion mapping were performed in patients under artificial respiration. Parenchymal xenon and iodine distribution were mapped and correlated with structural or vascular abnormalities. In all datasets, image quality was sufficient for a comprehensive image reading of the pulmonary CTA images, lung window images and pulmonary functional parameter maps and led to expedient results in each patient. With dual-source CT systems, DECT of the lung with iodine or xenon administration is technically feasible and makes it possible to depict the regional iodine or xenon distribution representing the local perfusion and ventilation. (orig.)

Definition, epidemiology and registries of pulmonary hypertension.

Science.gov (United States)

Awdish, R; Cajigas, H

2016-05-01

Pulmonary arterial hypertension (PAH) is a subcategory of pulmonary hypertension (PH) that comprises a group of disorders with similar pulmonary vascular pathology. Though PH is common, the estimated incidence of IPAH is 1-3 cases per million, making it a rare disease. The hemodynamic definition of PAH is a mean pulmonary artery pressure at rest >OR = 25 mm Hg in the presence of a pulmonary capillary wedge pressure pulmonary vascular resistance (PVR) greater than 3 WU. Specific maneuvers during right heart catheterization can be utilized to disclose vasoreactivity and heart failure with preserved ejection fraction, which have implications for management. The inherent complexity in studying a rare disease that exhibits clinical overlap with a common syndrome necessitated the creation of registries. These registries have been indispensable in the characterization and mapping of the natural history of the disease. Equations and risk calculators derived from registries have given clinicians a basis for risk stratification and prognostication. The sequential accumulation of data since the registries began in the 1980s allows for comparisons to be made. Patients who are differentiated by treatment eras and environments can be contrasted. Variability among inclusion criteria similarly allows for comparisons of these subpopulations. This article provides an overview of available registries, highlights insights provided by each and discusses key issues around the interpretation and extrapolation of data from PAH registries. Registries have allowed us to appreciate the improvement in survival afforded by modern therapy and enhanced detection of this disease. Moving forward, a more global approach to registries is needed, as is enhanced collaboration and centralization.

Vitamin D Deficiency in Patients with Tuberculosis

International Nuclear Information System (INIS)

Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.

2013-01-01

Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

Vitamin e intake, α-tocopherol levels and pulmonary function in children and adolescents with cystic fibrosis

NARCIS (Netherlands)

Woestenenk, Janna W.; Broos, Nancy; Stellato, Rebecca; Arets, Hubertus G M; Van Der Ent, Cornelis K.; Houwen, Roderick H J; Arets, HGM

2015-01-01

Pancreatic insufficiency cystic fibrosis (CF) patients receive vitamin E supplementation according to CF-specific recommendations in order to prevent deficiencies. It has been suggested that higher serum α-tocopherol levels could have protective effects on pulmonary function (PF) in patients with

Toward reassessing data-deficient species.

Science.gov (United States)

Bland, Lucie M; Bielby, Jon; Kearney, Stephen; Orme, C David L; Watson, James E M; Collen, Ben

2017-06-01

One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. © 2016 Society for Conservation Biology.

CT findings of pulmonary cryptococcosis in immunocompetent children

International Nuclear Information System (INIS)

Wang Bei; Peng Yun; Zhou Chunjun; Zhao Shunying

2012-01-01

Objective: The aim of our study was to study the CT findings of cryptococcosis in immunocompetent children. Methods: CT scan and clinical data of 21 immunocompetent children with proven pulmonary cryptococcosis were retrospectively collected and analyzed. Results: The CT scans demonstrated 1 mm subpleural nodule in the lingula of left lung in 1 patient and multiple nodules in 20 patients.Of 20 patients with multiple nodules, peripheral or subpleural distribution was found in 12 patients,and diffuse distribution in 8 patients. Of 20 patients with multiple nodules,Nodules of < 10 mm was found in 18 patients,< 3 mm in 14 patients, and > 10 mm in 2 patients. Round nodular with smooth margin was detected in 15 of 20 patients with multiple nodules. Lymphadenopathy was found in 17 patients including 3 patients with mild contrast enhancement and 2 patients with circular enhancement. Extrapulmonary lesions distributing in liver, spleen, kidney, and the nervous system were found in 14 patients. In follow-up, 1 patient died and 20 patients fully recovered. Conclusions: Pulmonary multiple nodules with lymphadenopathy is the characteristic CT findings in immunocompetent children with pulmonary cryptococcosis which is prone to involve multiple extra-pulmonary organs. (authors)

Aneurysms of proximal pulmonary arteries: CT diagnosis and preoperative assessment

International Nuclear Information System (INIS)

Iula, G.; Ziviello, R.; Del Vecchio, W.

1996-01-01

We reviewed our experience with proximal pulmonary artery aneurysm (PPAA) to determine whether accurate preoperative evaluation (crucial to differential diagnosis and surgical planning) had been obtained on the basis of CT study alone. Three patients with PPAA were studied with contrast-enhanced CT. We evaluated the size and shape of PPAAs, their proximal and distal extent, eventual presence of intraluminal thrombi, dissection, perianeurysmal fibrosis, and rupture. The results were compared with surgical findings. In two patients the aneurysm involved the pulmonary trunk and both the right and left arteries origin. In one patient the aneurysm extended from the left artery origin to the hilum of the left lung. Contrast-enhanced CT alone allows detection of aneurysm in the pulmonary trunk, in right or left pulmonary arteries with precise preoperative evaluation of the extent, size, shape, and complications. The CT imaging was unable to establish the etiologic origin and presence of small intimal tears in PPAA. (orig.)

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Shirai, Hidenori; Fujimori, Hiroaki [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Gunji, Akemi [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Maeda, Daisuke [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Hirai, Takahisa [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Radiation Oncology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Poetsch, Anna R. [ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Harada, Hiromi [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Yoshida, Tomoko [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minatoku, Tokyo 105-8512 (Japan); Sasai, Keisuke [Department of Radiation Oncology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555 (Japan); Masutani, Mitsuko, E-mail: mmasutan@ncc.go.jp [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

2013-05-24

Highlights: •Parg{sup −/−} ES cells were more sensitive to γ-irradiation than Parp-1{sup −/−} ES cells. •Parg{sup −/−} cells were more sensitive to carbon-ion irradiation than Parp-1{sup −/−} cells. •Parg{sup −/−} cells showed defects in DSB repair after carbon-ion irradiation. •PAR accumulation was enhanced after carbon-ion irradiation compared to γ-irradiation. -- Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg{sup −/−} and poly(ADP-ribose) polymerase-1 deficient (Parp-1{sup −/−}) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg{sup −/−} cells were more sensitive to γ-irradiation than Parp-1{sup −/−} cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg{sup −/−} cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg{sup −/−} ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1{sup −/−} cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg{sup −/−} ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg{sup −/−} cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1{sup −/−} cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation

International Nuclear Information System (INIS)

Shirai, Hidenori; Fujimori, Hiroaki; Gunji, Akemi; Maeda, Daisuke; Hirai, Takahisa; Poetsch, Anna R.; Harada, Hiromi; Yoshida, Tomoko; Sasai, Keisuke; Okayasu, Ryuichi; Masutani, Mitsuko

2013-01-01

Highlights: •Parg −/− ES cells were more sensitive to γ-irradiation than Parp-1 −/− ES cells. •Parg −/− cells were more sensitive to carbon-ion irradiation than Parp-1 −/− cells. •Parg −/− cells showed defects in DSB repair after carbon-ion irradiation. •PAR accumulation was enhanced after carbon-ion irradiation compared to γ-irradiation. -- Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg −/− and poly(ADP-ribose) polymerase-1 deficient (Parp-1 −/− ) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg −/− cells were more sensitive to γ-irradiation than Parp-1 −/− cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg −/− cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg −/− ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1 −/− cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg −/− ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg −/− cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1 −/− cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg −/− cells. The augmented

Computerized axial tomography of the chest for visualization of ''absent'' pulmonary arteries

International Nuclear Information System (INIS)

Sondheimer, H.M.; Oliphant, M.; Schneider, B.; Kavey, R.E.W.; Blackman, M.S.; Parker, F.B. Jr.

1982-01-01

To expand the search for central pulmonary arteries in six patients with absence of cardiac-pulmonary continuity, computerized axial tomography (CAT) of the chest was performed. The CAT scans were compared with previous arteriograms and pulmonary vein wedge angiograms. Three patients with type IV truncus arteriosus were studied, and none had a central, right or left pulmonary artery on CAT scan. However, two patients with tetralogy of Fallot with pulmonary atresia and a patent ductus arteriosus to the right lung demonstrated the presence of a left pulmonary artery. In addition, one child with truncus arteriosus with ''absent'' left pulmonary artery demonstrated a left pulmonary artery on the CAT scan. The CAT scan may therefore enhance our ability to search for disconnected pulmonary arteries in children with complex cyanotic congenital heart disease

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

Science.gov (United States)

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combined effects of enhanced UV-B radiation and nitrogen deficiency on the growth, composition and photosynthesis of rye (Secale cereale)

International Nuclear Information System (INIS)

Deckmyn, G.; Impens, I.

1997-01-01

The interactive effects of N-deficiency and enhanced UV-B radiation on growth, photosynthesis and pigmentation of rye were studied. The plants were grown for 5 weeks in growth chambers with high (700 μmol m -2 s -2 ) irradiance levels. A 30% difference in UV-B at plant level was achieved by using different thicknesses of UV-B transparent Plexiglass. One half of the plants received optimal N nutrition, while the other received half of this dose. Both enhanced UV-B and N deficiency strongly decreased production (from 24–33%). The combined effect was additive (no interaction) on most parameters, including total dry weight production which was 52% lower than in the control series. Significant interaction was found on the root/shoot ratio. While reduced N supply induced an increase in the ratio at normal UV-B irradiation, under the increased UV-B, N deficiency had no effect on the root/shoot ratio. The reduced biomass due to UV-B was clearly correlated to a reduction in photosynthesis. At optimal N supply the plants increased the production of protective pigments in response to UV-B, but at reduced N supply this response was lacking. The increased N content of the high UV-B/high N plants could be a result of increased flavonoid production as well as changes in light penetration in the canopy. (author)

Differentiation of benign and malignant solitary pulmonary nodules : value of contrast-enhanced dynamic MR imaging

International Nuclear Information System (INIS)

Kim, Jeong Ho; Kim, Hyung Jin; Han, Heon; Lee, Hong Lyeol; Kim, Kwang Ho; Suh, Chang Hae

1999-01-01

To evaluate the usefulness of contrast-enhanced dynamic MR imaging for differentiation of benign and malignant solitary pulmonary nodules (SPNs). Twenty-three patients with histologically or radiologically provened SPNs smaller than 40mm (14 benign, 9 malignant) underwent MR examination using the breath-hold fast multiplanar spoiled gradient echo (FMPSPGR) technique. Pre-enhancement MR examination was followed by serial scans obtained at one-minute intervals, beginning one-minute after the onset of bolus injection of paramagnetic contrast agent for a total of five scans. Signal intensities of SPNs were measured from pre- and post-contrast enhanced MR images and peak percentage increase in signal intensity (p%SI) was calculated. Mean percentage increase in signal intensity (m%SI) was also calculated and the time-m%SI curve was plotted. The enhancement patterns of SPNs were classified as homogeneous, peripheral rim-like, inhomogeneous, or no (or minimal) enhancement. We compared differences in p%SI, the pattern of the time-m%SI curve, and the pattern of enhancement between benign and malignant SPNs. On dynamic MR images, alignant SPNs (n=9) showed a significantly higher p%SI than benign SPNs (n=14) (malignant : mean 120.6, range 81.8-171.6; benign : mean 29.5, range 3.7-78.9)(p<0.0001). With 80 p%SI as the threshold for malignancy-positive, both sensitivity and specificity were 100%. The m%SI of malignant SPNs rapidly increased at one minute after enhancement and decreased gradually thereafter, whereas that of benign SPNs increased more slowly to form a plateau. Eighty-nine percent (8/9) of malignant SPNs showed homogeneous enhancement. In contrast, among benign SPNs, peripheral rim-like enhancement and no (or minimal) enhancement occurred in the same proportion of cases : 50%(7/14). The superb demonstration of different enhancement characteristics obtained using dynamic contrast-enhanced MR imaging is useful to discriminate malignant from benign SPNs

Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA

International Nuclear Information System (INIS)

Lorino, A.M.; Meignan, M.; Bouissou, P.; Atlan, G.

1989-01-01

The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99m Tc-labeled diethylenetriaminepentaacetate ( 99m Tc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99m Tc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O 2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency

Pulmonary complications of endocrine and metabolic disorders.

Science.gov (United States)

Milla, Carlos E; Zirbes, Jacquelyn

2012-03-01

There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diagnostic value of contrast-enhanced dynamic CT in predicting the malignancy of solitary pulmonary nodules

International Nuclear Information System (INIS)

Goo, Hyun Woo; Song, Koun Sik; Lee, Eun Hye; Kim, Ji Hoon; Lee, Jin Seong; Lim, Tae Hwan

1997-01-01

To determine whether the maximal enhancement time in dynamic CT is different between benign and malignant solitary pulmonary nodules (SPN)s, and to evaluate the value of densitometry on dynamic CT in predicting the malignancy of SPN. Fifty-six patients with SPN of less than 4cm in diameter as seen on chest radiograph and SPN without benign pattern of calcification or fat, as seen on pre-enhance-ment spiral CT scans were included in this study. SPN with small cavitation sufficient to measure CT density, were also included. Thirty-four SPNs were diagnosed pathologically or radiologically as 20 malignant nodules and 14 benign nodules. Dynamic CT was performed by two techniques after injection of 50ml of nonionic contrast media at the rate of 2ml/sec. In 28 patients, incremental dynamic CT was performed before and of 15 seconds, 1 minute, 2 minutes, 3 minutes, and 4 minutes after injection of contrast media during shallow respiration. In 28 patients, double spiral CT was performed 2 minutes and 3 minutes after injection of contrast media during single breath hold. CT readings were taken at the central portion of SPNs, with a circular region of interest. The degree and time of maximal enhancement were recorded. In dynamic CT the maximal enhancement time of SPNs was not significantly different between malignant (2.73±1.27 minute) and benign nodules (2.56±1.24 minute). The enhancement of malignant nodules was significantly greater (21.42±12.17 HU) than of benign nodules (5.15±5.25 HU) (p<.0001). In dynamic CT of SPNs, there is no difference in maximal enhancement time between benign and malignant nodules;enhancement of the latter is significantly greater than that of the former. Maximal enhancement greater than 15 HU can be a good predictor of malignancy of SPNs

A comparative study of pulmonary hypoperfusion secondary to cancerous invasion of central pulmonary artery in lung cancer with CT and DSA

International Nuclear Information System (INIS)

Guo Dajing; Miao Jingtao; Lu Wusheng; Bai Hongli

2003-01-01

Objective: To study CT features of pulmonary hypoperfusion in lung cancer with cancerous invasion of central pulmonary artery (CICPA) and the diagnostic value of CT. Methods: The pre-operative pulmonary DSA and contrast-enhanced spiral CT (including HRCT) findings in 20 cases of lung cancer with CICPA were carried out prospectively and comparatively. On DSA and CT, the distribution and quantitative variation of subpleural terminal pulmonary arterioles (pulmonary vessel signs), the filling degree of lung capillary, the post-contrast density changes of lung parenchyma, and the fluctuations of the time-density curve (pulmonary parenchymal signs) were blindly observed. The CT and DSA findings and their consistence were analyzed statistically. The diagnostic values of CT in secondary pulmonary hypoperfusion in lung cancer with CICPA were evaluated. Results: There were 30 lobar arteries with cancerous invasion among the 20 cases and 90% (27/30) of them presented pulmonary hypoperfusion on DSA. For diagnosing pulmonary hypoperfusion, CT had a sensitivity of 78%(21/27), a specificity of 100% (3/3), and an accuracy of 80%(24/30). There were no statistical correlation between pulmonary hypoperfusion and the degree of central pulmonary artery (CPA) stenosis (r s =0.40, P=0.073). Pulmonary vessel signs on CT had a good consistence with that on DSA (Kappa=0.69, P<0.001), while that of pulmonary parenchymal signs was lower (Kappa=0.37, P=0.011). Conclusion: Pulmonary hypoperfusion is one of the common findings in lung cancer with CICPA. CT is of great value in qualitative diagnosis on it, while for quantitative diagnosis, its value is limited to a certain degree

ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

Science.gov (United States)

Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

2018-05-01

PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Pulmonary complications in HIV-positive patients with only moderately pronounced immune deficiency

International Nuclear Information System (INIS)

Jacobi, V.; Kirchner, J.; Thalhammer, A.

1995-01-01

Rare diseases like Kaposi's sarcoma or uncharacteristic symptoms and signs of common disorders of the lungs like diffuse pneumococcal pneumonia or pulmonary involvement by lymphomas require refined X-ray measures, which are mostly broadened to include CT. An adequate knowledge of typical findings (signs of bronchiolitis in atypical pneumococcal pneumonia or pneumonia caused by Haemophilus influenza) often permits an at-a-glance diagnosis without the need of any further diagnostic tools. (orig./MG) [de

Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension.

Science.gov (United States)

Kumar, Vasanth H; Swartz, Daniel D; Rashid, Nasir; Lakshminrusimha, Satyan; Ma, Changxing; Ryan, Rita M; Morin, Frederick C

2010-09-01

Aerosolized prostacyclin (PGI2) produces selective pulmonary vasodilation in patients with pulmonary hypertension (PH). The response to PGI2 may be increased by phosphodiesterase type 3 inhibitors such as milrinone. We studied the dose response effects of aerosolized PGI2 and aerosolized milrinone both alone and in combination on pulmonary and systemic hemodynamics in newborn lambs with Nomega-nitro-L-arginine methyl ester (L-NAME)-induced PH. We hypothesized that coaerosolization of PGI2 with milrinone would additively decrease pulmonary vascular resistance (PVR), prolong the duration of action of PGI2, and selectively dilate the pulmonary vasculature. Near-term lambs were delivered by C-section and instrumented and PH was induced by L-NAME (bolus 25 mg/kg; infusion 10 mg.kg(-1).h(-1)) and indomethacin. In the first set of experiments, PGI2 was aerosolized at random doses of 2, 20, 100, 200, 500, and 1,000 ng.kg(-1).min(-1) followed by milrinone at doses of 0.1, 1, and 10 microg.kg(-1).min(-1) over 10 min. In the second set of experiments, milrinone at 1 microg.kg(-1).min(-1) was aerosolized in combination with PGI2 at doses of 20, 100, and 200 ng.kg(-1).min(-1) over 10 min. Pulmonary arterial pressures (PAP) and PVR decreased significantly with increasing doses of aerosolized PGI2 and milrinone. The combination of PGI2 and milrinone significantly reduced PAP and PVR more than either of the drugs aerosolized alone. Addition of milrinone significantly increased the duration of action of PGI2. When aerosolized independently, PGI2 and milrinone selectively dilated the pulmonary vasculature but the combination did not. Milrinone enhances the vasodilatory effects of PGI2 on the pulmonary vasculature but caution must be exercised regarding systemic hypotension.

Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

Science.gov (United States)

Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

2012-04-01

Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

Localization fibrosing mediastinitis causing pulmonary infraction: A case report

Energy Technology Data Exchange (ETDEWEB)

Sur, Young Keun; Kim, Eun Young; Kang, Doo Kyoung; Park, Kyung Joo; Koh, Young Wha; Sun, Joo Sung [Ajou University School of Medicine, Suwon (Korea, Republic of)

2016-06-15

A 44-year-old female patient visited our emergency room for hemoptysis and refractory chest wall pain of 2 months duration. She had no history of smoking or other medical conditions. Chest CT scan showed homogenously enhancing soft tissue mass without calcification at the left pulmonary hilum. Encasing and compression of the left lower pulmonary artery by the mass had resulted in pulmonary infarction in the left lower lobe. Laboratory tests for tuberculosis, fungus, and vasculitis were all negative. The patient underwent surgical biopsy and resection of infarcted left lower lobe that was histopathologically confirmed as fibrosing mediastinitis. Herein, we reported a rare case of surgically confirmed and treated localized fibrosing mediastinitis causing pulmonary infarction.

CTPA for the diagnosis of acute pulmonary embolism during pregnancy

Energy Technology Data Exchange (ETDEWEB)

Schaefer-Prokop, C. [Dept. of Radiology, Academic Medical Center, Amsterdam (Netherlands); Prokop, M. [Dept. of Radiology, Utrecht Medical Center (Netherlands)

2008-12-15

CT pulmonary angiography (CTPA) has been suggested by the Fleischner society as the first test following a negative leg ultrasound in pregnant patients with suspected pulmonary embolism. This editorial discusses the use of CTPA as a diagnostic tool in pregnant women and comments on the need for specifically adapting CT protocols during pregnancy in the light of new research describing a substantial number of non-diagnostic examinations in pregnant women if routine scanning protocols are used for CTA of the pulmonary arteries. Potential reasons for these high numbers of insufficient examinations are physiological changes occurring during pregnancy that lead to a hyperdynamic circulation, which reduces average enhancement of the pulmonary vasculature. In addition, there are possible breathing-related effects that include an increased risk for Valsalva manoeuvre with devastating effects for pulmonary vascular enhancement. Techniques to overcome these problems are discussed: bolus triggering with short start delays, high flow rates or high contrast medium concentration, preferential use of fast CT systems and the use of low kVp CT techniques. CT data acquisition during deep inspiration should be avoided and shallow respiration may be considered as an alternative to suspended breathing in this patient group. All these factors can contribute to optimization of the quality of pulmonary CTA in pregnant patients. It is time now to adapt our protocols and provide optimum care for this sensitive patient group.

Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma in 41 patients

Energy Technology Data Exchange (ETDEWEB)

Ma, Huali; Wu, Yaopan [Department of Radiology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Lin, Yongbin [Department of Thoracic Surgery, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Cai, Qingqing [Department of Medical Oncology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Ma, Guowei [Department of Thoracic Surgery, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Liang, Ying, E-mail: liangying@sysucc.org.cn [Department of Medical Oncology, State Key Laboratory of Oncology in South China/Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China)

2013-08-15

Purpose: To assess the computed tomography (CT) findings of primary pulmonary lymphoepithelioma-like carcinoma (LELC). Materials and methods: Clinical information and CT findings of 41 patients with pulmonary LELC were reviewed. CT images of 2 or 5 mm thickness were obtained with a pre-treatment CT and were jointly evaluated by two radiologists. Results: Thirty central tumors and 11 peripheral tumors with diameters ranging from 1.0 to 8.7 cm (mean, 4.1 ± 1.9 cm) were identified. Central tumors appeared to be larger than peripheral tumors (P = 0.017). Tumors occurred more frequently in right middle lobe (31.7%) and left lower lobe (29.3%). CT findings of patients with early stage were similar to those observed in patients with advanced stage except that lymphadenopathy was significantly more common in patients with advanced stage. CT findings of pulmonary LELC consisted of well defined border (63.4%), lobulation (78.0%), vascular or bronchial encasement (43.9%), obstructive pneumonia (41.5%), pleural effusion (12.2%) and calcification (4.9%). On contrast-enhanced CT scans, inhomogeneously enhanced tumors were significantly larger than homogeneously enhanced tumors (P < 0.001). Lymphadenopathy was seen in 28 patients, and lymph nodes with homogeneous enhancement were observed in 24/28 patients. Enlarged lymph nodes were more frequently occurred in peribronchial or hilar nodes (53.7%), subcrinal nodes (39.0%), right lower paratracheal nodes (31.7%) and right upper paratracheal nodes (22.0%). Conclusion: Pulmonary LELC usually appeared as a large, central, well defined and lobulated tumor with vascular or bronchial encasement and obstructive pneumonia. Calcification was rare in pulmonary LELC. Lymphadenopathy was common, usually with homogeneous enhancement.

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

International Nuclear Information System (INIS)

Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

2015-01-01

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

Energy Technology Data Exchange (ETDEWEB)

Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

2015-09-25

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma

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Mogilevski Grigori

2004-09-01

Full Text Available Abstract Background Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. Methods Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6 or non-alpha-1 antitrypsin deficiency emphysema (n = 34 or wedge resection for hamartochondroma (n = 14 were examined by transmission electron microscopy and PCR. Results In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. Conclusions These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process

Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

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Christopher Coleman

2014-01-01

Full Text Available Pulmonary hyalinizing granuloma (PHG is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP in our patient, may also favor HG. In this case report we find an association between PHG and ITP.

Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

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Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi

2012-01-01

Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.

Diagnosis of Grave's disease with pulmonary hypertension on chest CT.

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Lee, Hwa Yeon; Yoo, Seung Min; Kim, Hye Rin; Chun, Eun Ju; White, Charles S

To evaluate the diagnostic accuracy of chest CT findings to diagnose Grave's disease in pulmonary hypertension. We retrospectively evaluated chest CT and the medical records of 13 patients with Grave's disease with (n=6) or without pulmonary hypertension (n=7) and in 17 control patients. Presence of iso-attenuation of diffusely enlarged thyroid glands compared with adjacent neck muscle on non-enhanced CT as a diagnostic clue of Grave's disease, and assessment of pulmonary hypertension on CT has high diagnostic accuracy. Chest CT has the potential to diagnose Grave's disease with pulmonary hypertension in the absence of other information. Copyright © 2017 Elsevier Inc. All rights reserved.

IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.

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Paméla Gasse

Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+ γδ T cells and to a lesser extent by CD4αβ(+ T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

γδ T cells are required for pulmonary IL-17A expression after ozone exposure in mice: role of TNFα.

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Joel A Mathews

Full Text Available Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24-72 h. We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ-/- to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ-/- mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ-/- mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ-/- versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung.

[Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

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Ponomarev, R V; Model, S V; Averbukh, O M; Gavrilov, A M; Galstyan, G M; Lukina, E A

Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

Pulmonary CT angiography protocol adapted to the hemodynamic effects of pregnancy.

LENUS (Irish Health Repository)

Ridge, Carole A

2012-02-01

OBJECTIVE: The purpose of this study was to compare the image quality of a standard pulmonary CT angiography (CTA) protocol with a pulmonary CTA protocol optimized for use in pregnant patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS: Forty-five consecutive pregnant patients with suspected PE were retrospectively included in the study: 25 patients (group A) underwent standard-protocol pulmonary CTA and 20 patients (group B) were imaged using a protocol modified for pregnancy. The modified protocol used a shallow inspiration breath-hold and a high concentration, high rate of injection, and high volume of contrast material. Objective image quality and subjective image quality were evaluated by measuring pulmonary arterial enhancement, determining whether there was transient interruption of the contrast bolus by unopacified blood from the inferior vena cava (IVC), and assessing diagnostic adequacy. RESULTS: Objective and subjective image quality were significantly better for group B-that is, for the group who underwent the CTA protocol optimized for pregnancy. Mean pulmonary arterial enhancement and the percentage of studies characterized as adequate for diagnosis were higher in group B than in group A: 321 +\\/- 148 HU (SD) versus 178 +\\/- 67 HU (p = 0.0001) and 90% versus 64% (p = 0.05), respectively. Transient interruption of contrast material by unopacified blood from the IVC was observed more frequently in group A (39%) than in group B (10%) (p = 0.05). CONCLUSION: A pulmonary CTA protocol optimized for pregnancy significantly improved image quality by increasing pulmonary arterial opacification, improving diagnostic adequacy, and decreasing transient interruption of the contrast bolus by unopacified blood from the IVC.

Pulmonary embolism and pelvic-lower limb deep venous thrombosis: initial experience with magnetic resonance angiography

International Nuclear Information System (INIS)

Jiang Tao; Qiu Chuanya; Jiang Hua

2004-01-01

Objective: To evaluate the usefulness of combined three-dimensional (3D) and two-dimensional (2D) contrast enhanced magnetic resonance angiography (CE-MRA) for checking the thrombus embolism of different positions within single examination on the pulmonary artery and pelvic-lower limb deep veins. Methods: Fifteen patients with suspected pulmonary embolism and pelvic-lower limb deep venous thrombosis (DVT) were evaluate with combined 3D MRA and 2D CE-MRA. 3D spoiled gradient-recalled-echo bolus chase MR angiograms were obtained in four stations from the pulmonary artery to the ankle. Thereafter, 3D CE MRA was reversely scanned from the ankle to the pelvic. 2D contrast-enhanced MRI was obtained in pelvis, thigh, and calf. Pulmonary CT angiography (CTA) and/or DSA were performed in 15 patients, and duplex ultrasonography of lower-limb vein was performed in 12 patients. Results: Of the 15 cases, acceptable imaging of pulmonary vessel was acquired with 3D CE-MRA in 12 cases. The signal intensity was lower in the deep iliac vein and lower extremities than that in the artery, but vein frame was distinct after post processing. The artery and deep vein were clearly revealed with contrast enhanced FSPGR sequence in 15 cases. 3D CD-MRA imaging disclosed pulmonary embolism in fourteen patients and pelvis-lower limb DVT with multi-place involvement in nine patients. 2D contrast-enhanced MR imaging proved DVT in pelvis-lower limb. 2D contrast-enhanced FSPGR sequence was a complementation of 3D CE-MRA and it had larger scan field. Thrombus presented as low signals and eccentral or intraluminal filling defect. Local caliber of vein thrombus in 6 cases was evidently broadened. Conclusion: Within only one MR examination procedure, it is capable of examining the pulmonary embolism and DVT of pelvis-lower limb with combined 3D MRA and 2D contrast enhanced MR. The results are promising as a non-invasion 'on-stop shopping' tool in the evaluation of thromboembolic disease

Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets

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Learta Oruqaj

2016-10-01

Full Text Available Aims: Parathyroid hormone-related protein (PTHrP is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined. Materials and methods: C57 bl/6 mice were randomized to either normal diet or high fat diet at an age of 6 weeks. Seven months later, the mice were euthanized and the lung was removed and frozen in fluid nitrogen until use. Samples were analyzed by real-time RT-PCR and western blot. Leptin deficient mice were used to investigate the effect of leptin on pulmonary expression of PTHrP more directly. A subgroup of mice with and without high fat diet underwent in vivo ischemia (45 min and reperfusion (4 weeks. Finally, experiments were repeated with prolonged high-fat diet. Key findings: High fat diet increased plasma leptin levels by 30.4% and the pulmonary mRNA expression of PTHrP (1,447-fold, PTH-1 receptor (4.21-fold, and PTHrP-downstream targets ADRP (7.54-fold and PPARγ (5.27-fold. Pulmonary PTHrP expression was reduced in leptin deficient mice by 88% indicating leptin dependent regulation. High fat diet further improved changes in pulmonary adaptation caused by ischemia/reperfusion (1.48-fold increased PTH-1 receptor protein expression. These effects were lost during prolonged high fat diet. Significance: This study established that physiological regulation of leptin plasma levels by high fat diet affects the pulmonary PTHrP expression and of PTHrP downstream targets. Modification of pulmonary expression of PTH-1 receptors by high fat diet after myocardial infarction suggests that the identified interaction may

Pulmonary artery-to-pulmonary artery anastomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension

International Nuclear Information System (INIS)

Hodson, J.; Graham, A.; Hughes, J.M.B.; Gibbs, J.S.R.; Jackson, J.E.

2006-01-01

AIM: To describe direct pulmonary artery-to-pulmonary artery anastomoses seen at pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension and discuss their possible significance. MATERIALS AND METHODS: Between 1 August 2000 and 31 July 2004 43 patients (male-to-female ratio 25:18) with a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) underwent selective pulmonary angiography to assess the extent of disease and suitability for surgical pulmonary endarterectomy. The mean pulmonary artery pressure ranged from 27-84 mmHg (average of 51 mmHg). Selective bilateral digital subtraction pulmonary angiograms performed in all individuals were reviewed for the presence of intrapulmonary collaterals. RESULTS: In 15 of the 43 patients (male-to-female ratio =7:8) definite (n=12) or probable (n=3) pulmonary artery-to-pulmonary artery anastomoses were demonstrated. Of the remaining 28 patients in whom intrapulmonary collaterals were not seen it was felt that in 16 the angiograms were of insufficient diagnostic quality (grades 4-5) to exclude their presence. Twelve patients, eight of whom had angiograms of sufficient diagnostic quality (grades 1-3), demonstrated one or more areas of luxury perfusion but intrapulmonary collaterals were not seen. CONCLUSION: Direct pulmonary artery-to-pulmonary artery anastomoses were demonstrated in patients with chronic thromboembolic pulmonary hypertension, which to our knowledge have not been previously described. The importance of these collateral vessels is unclear but they may play a role in the maintenance of pulmonary parenchymal viability in patients with chronic pulmonary embolic disease. The rate of development of these collaterals and their prognostic significance in patients with chronic thromboembolic pulmonary hypertension are areas worthy of further study

Pulmonary artery-to-pulmonary artery anastomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension

Energy Technology Data Exchange (ETDEWEB)

Hodson, J. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Graham, A. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Hughes, J.M.B. [Department of Respiratory Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Gibbs, J.S.R. [Department of Cardiology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Jackson, J.E. [Department of Imaging, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London (United Kingdom)]. E-mail: jejackson@hhnt.org

2006-03-15

AIM: To describe direct pulmonary artery-to-pulmonary artery anastomoses seen at pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension and discuss their possible significance. MATERIALS AND METHODS: Between 1 August 2000 and 31 July 2004 43 patients (male-to-female ratio 25:18) with a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) underwent selective pulmonary angiography to assess the extent of disease and suitability for surgical pulmonary endarterectomy. The mean pulmonary artery pressure ranged from 27-84 mmHg (average of 51 mmHg). Selective bilateral digital subtraction pulmonary angiograms performed in all individuals were reviewed for the presence of intrapulmonary collaterals. RESULTS: In 15 of the 43 patients (male-to-female ratio =7:8) definite (n=12) or probable (n=3) pulmonary artery-to-pulmonary artery anastomoses were demonstrated. Of the remaining 28 patients in whom intrapulmonary collaterals were not seen it was felt that in 16 the angiograms were of insufficient diagnostic quality (grades 4-5) to exclude their presence. Twelve patients, eight of whom had angiograms of sufficient diagnostic quality (grades 1-3), demonstrated one or more areas of luxury perfusion but intrapulmonary collaterals were not seen. CONCLUSION: Direct pulmonary artery-to-pulmonary artery anastomoses were demonstrated in patients with chronic thromboembolic pulmonary hypertension, which to our knowledge have not been previously described. The importance of these collateral vessels is unclear but they may play a role in the maintenance of pulmonary parenchymal viability in patients with chronic pulmonary embolic disease. The rate of development of these collaterals and their prognostic significance in patients with chronic thromboembolic pulmonary hypertension are areas worthy of further study.

High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

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Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

2014-10-01

Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency.

Dual-energy MDCT: Comparison of pulmonary artery enhancement on dedicated CT pulmonary angiography, routine and low contrast volume studies

Energy Technology Data Exchange (ETDEWEB)

Godoy, Myrna C.B., E-mail: migbarco@gmail.com [New York University Langone Medical Center, Department of Radiology, New York, NY (United States); University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Heller, Samantha L.; Naidich, David P.; Assadourian, Bernard [New York University Langone Medical Center, Department of Radiology, New York, NY (United States); Leidecker, Christianne [Siemens Medical Solutions, Malvern, PA (United States); Schmidt, Bernhard [Siemens Healthcare, Forchheim (Germany); Vlahos, Ioannis [New York University Langone Medical Center, Department of Radiology, New York, NY (United States); St. George' s Hospital NHS Trust, London (United Kingdom)

2011-08-15

Purpose: The aim of this study was (a) to compare arterial enhancement in simultaneously acquired high- and low-kilovoltage images; and (b) to determine whether low tube-voltage imaging would permit PE evaluation on routine chest CT studies or CTPA studies performed with a low volume of contrast media. Materials and methods: We compared 20 CTPA studies (CTPA group), 20 routine thoracic CT studies (RT group) and 10 CTPA studies performed with reduced volume of contrast media (RC group). HU values were measured in all groups at 80 kVp and 140 kVp images in multiple pulmonary arterial segments bilaterally. The diagnostic quality of the central and peripheral vascular enhancement and the image noise were evaluated at both energies using a five-point scale. Results: For all patients, the mean CT attenuation values were greater at 80 kVp than 140 kVp images (p < 0.001). At 80 kVp, CTPA group attenuation values were greater than RT group (p = 0.03) with a similar trend at 140 kVp (p = 0.08). At both 140 kVp and 80 kVp, CTPA group attenuation values were greater than RC group (p = 0.02 and p = 0.03, respectively). Qualitative analysis showed that at 140 kVp CTPA studies had better global image quality scores than RT (p = 0.003) and RC (p = 0.001) groups. However, at 80 kVp, there was no significant difference of global image quality between CTPA and the other groups (p = 0.4 and p = 0.5, respectively). Although measurable image noise was greater at 80 kVp than 140 kVp (p < 0.001), qualitative analysis revealed lower image noise at 80 kVp images. Conclusion: DECT at 80 kVp increases arterial enhancement in both CTPA and routine studies. For routine studies this results in central and peripheral enhancement quality equivalent to that of CTPA studies. Low tube-voltage imaging allows marked contrast volume reduction for CTPA. In selected cases, satisfactory lower radiation dose CT might be achievable using lower kVp imaging alone.

Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction

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Juan M. Povedano

2015-07-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a degenerative disease of the lungs with an average survival post-diagnosis of 2–3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells. We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments.

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

Science.gov (United States)

Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

2016-01-01

The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

Dual-energy CT in the evaluation of solitary pulmonary nodules by virtual non-enhanced images: initial experience

International Nuclear Information System (INIS)

Guo Xing; Ding Wei; Qin Huijuan

2011-01-01

Objective: To determine the accuracy and radiation dose of dual-energy computed tomography (CT) in evaluating solitary pulmonary nodules (SPNs) by virtual non-enhanced images. Methods: Sixty-one patients with SPNs including 39 malignant and 18 benign nodules proved by pathology underwent DECT scans. The CT values of SPNs on enhanced weighted average and virtual non-enhanced images were compared by using Liver VNC processing unit in terms of their diagnostic accuracy for distinguishing malignant and benign nodules with a 20 HU threshold. Diagnostic accuracy was compared. In 28 patients of all patients, image noise and quality score of the non-enhanced and virtual non-enhanced images were compared, and radiation doses of each patient were recorded. The paired t test was used to analyze the noise difference between the plain scan and virtual non-enhanced scan. The Mann-Whitney U test. was used to analyze statistically significant differences of the image quality score and radiation dose between the non-enhanced scan and virtual non-enhanced scan. Results: The sensitivity, specificity and accuracy for distinguishing benign and malignant nodules by using the virtual non-enhanced image of were 89.7% (35/39), 72.2% (13/18), 84.2% (48/57) respectively. The noise of common CT and virtual non- enhanced images were (8.49±1.94) HU and (10.14±2.18) HU, and there were statistically difference (t=9.45, P 0.05). The radiation doses of common CT and DECT were (3.72±0.48) mSv and (3.78±0.45) mSv, and there were no statistical difference (U= 350.50, P>0.05). Conclusion: DECT by using virtual non-enhanced images is useful tool to distinguish the benign and malignant SPN without additional radiation dose. (authors)

A novel potassium deficiency-induced stimulon in Anabaena torulosa

Indian Academy of Sciences (India)

Unknown

torulosa and of nine proteins in Escherichia coli. These were termed potassium deficiency-induced proteins or. PDPs and constitute hitherto unknown potassium deficiency–induced stimulons. Potassium deficiency also enhanced the synthesis of certain osmotic stress-induced proteins. Addition of K+ repressed the ...

Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

Science.gov (United States)

Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

2015-01-01

Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

Science.gov (United States)

Frank, Benjamin S.

2018-01-01

Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed. PMID:29570688

Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

Science.gov (United States)

Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

2009-10-01

Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

Science.gov (United States)

Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

2015-05-01

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hematopoietic studies in vitamin A deficiency.

Science.gov (United States)

Hodges, R E; Sauberlich, H E; Canham, J E; Wallace, D L; Rucker, R B; Mejia, L A; Mohanram, M

1978-05-01

Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

Energy Technology Data Exchange (ETDEWEB)

Chung, Myung Jin; Goo, Jin Mo E-mail: jmgoo@plaza.snu.ac.kr; Im, Jung-Gi

2004-11-01

Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia.

Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Chung, Myung Jin; Goo, Jin Mo; Im, Jung-Gi

2004-01-01

Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia

Pulmonary Hypertension Associated with Idiopathic Pulmonary Fibrosis: Current and Future Perspectives

Directory of Open Access Journals (Sweden)

Scott D. Collum

2017-01-01

Full Text Available Pulmonary hypertension (PH is commonly present in patients with chronic lung diseases such as Chronic Obstructive Pulmonary Disease (COPD or Idiopathic Pulmonary Fibrosis (IPF where it is classified as Group III PH by the World Health Organization (WHO. PH has been identified to be present in as much as 40% of patients with COPD or IPF and it is considered as one of the principal predictors of mortality in patients with COPD or IPF. However, despite the prevalence and fatal consequences of PH in the setting of chronic lung diseases, there are limited therapies available for patients with Group III PH, with lung transplantation remaining as the most viable option. This highlights our need to enhance our understanding of the molecular mechanisms that lead to the development of Group III PH. In this review we have chosen to focus on the current understating of PH in IPF, we will revisit the main mediators that have been shown to play a role in the development of the disease. We will also discuss the experimental models available to study PH associated with lung fibrosis and address the role of the right ventricle in IPF. Finally we will summarize the current available treatment options for Group III PH outside of lung transplantation.

Pulmonary Artery Aneurysm/Pseudoaneurysm, a Delayed Complication of Lung Abscess: A Case Report.

Science.gov (United States)

Oguma, Tsuyoshi; Morise, Masahiro; Harada, Kazuki; Tanaka, Jun; Sato, Masako; Horio, Yukihiro; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Hayama, Naoki; Aoki, Takuya; Urano, Tetsuya; Ito, Chihiro; Koizumi, Jun; Asano, Koichiro

2015-09-20

Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection. A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan. Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels.

Chronic thromboembolic pulmonary hypertension - assessment by magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Kreitner, Karl-Friedrich; Kunz, R.P.; Oberholzer, Katja; Neeb, Daniel; Gast, Klaus K.; Dueber, Christoph [Johannes-Gutenberg-University, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Ley, Sebastian [Johannes-Gutenberg-University, Department of Diagnostic and Interventional Radiology, Mainz (Germany); German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Heussel, Claus-Peter [Johannes-Gutenberg-University, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Chest Clinic at University of Heidelberg, Department of Radiology, Heidelberg (Germany); Eberle, Balthasar [Johannes-Gutenberg-University, Department of Anesthesiology, Mainz (Germany); Inselspital, Department of Anesthesiology, Bern (Switzerland); Mayer, Eckhard [Johannes-Gutenberg-University, Department of Heart, Thorax and Vascular Surgery, Mainz (Germany); Kauczor, Hans-Ulrich [German Cancer Research Center, Department of Radiology, Heidelberg (Germany)

2007-01-15

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease that has been ignored for a long time. However, with the development of improved therapeutic modalities, cardiologists and thoracic surgeons have shown increasing interest in the diagnostic work-up of this entity. The diagnosis and management of chronic thromboembolic pulmonary hypertension require a multidisciplinary approach involving the specialties of pulmonary medicine, cardiology, radiology, anesthesiology and thoracic surgery. With this approach, pulmonary endarterectomy (PEA) can be performed with an acceptable mortality rate. This review article describes the developments in magnetic resonance (MR) imaging techniques for the diagnosis of chronic thromboembolic pulmonary hypertension. Techniques include contrast-enhanced MR angiography (ce-MRA), MR perfusion imaging, phase-contrast imaging of the great vessels, cine imaging of the heart and combined perfusion-ventilation MR imaging with hyperpolarized noble gases. It is anticipated that MR imaging will play a central role in the initial diagnosis and follow-up of patients with CTEPH. (orig.)

Chronic thromboembolic pulmonary hypertension - assessment by magnetic resonance imaging

International Nuclear Information System (INIS)

Kreitner, Karl-Friedrich; Kunz, R.P.; Oberholzer, Katja; Neeb, Daniel; Gast, Klaus K.; Dueber, Christoph; Ley, Sebastian; Heussel, Claus-Peter; Eberle, Balthasar; Mayer, Eckhard; Kauczor, Hans-Ulrich

2007-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease that has been ignored for a long time. However, with the development of improved therapeutic modalities, cardiologists and thoracic surgeons have shown increasing interest in the diagnostic work-up of this entity. The diagnosis and management of chronic thromboembolic pulmonary hypertension require a multidisciplinary approach involving the specialties of pulmonary medicine, cardiology, radiology, anesthesiology and thoracic surgery. With this approach, pulmonary endarterectomy (PEA) can be performed with an acceptable mortality rate. This review article describes the developments in magnetic resonance (MR) imaging techniques for the diagnosis of chronic thromboembolic pulmonary hypertension. Techniques include contrast-enhanced MR angiography (ce-MRA), MR perfusion imaging, phase-contrast imaging of the great vessels, cine imaging of the heart and combined perfusion-ventilation MR imaging with hyperpolarized noble gases. It is anticipated that MR imaging will play a central role in the initial diagnosis and follow-up of patients with CTEPH. (orig.)

False-positive radioactive iodine uptake mimicking miliary lung metastases in a patient affected by papillary thyroid cancer and IgA deficiency

Energy Technology Data Exchange (ETDEWEB)

Demidowich, Andrew Paul; Reynolds, James C. [National Institutes of Health, Bethesda (United States); Kundu, Amartya [Dept. of MedicineUniversity of Massachusetts Medical School, Worcester (United States); Celi, Francesco S. [Div. of Endocrinology and MetabolismVirginia Commonwealth UniversityRichmond (United States)

2016-09-15

A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). Follow-up {sup 123}I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial {sup 123}I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization. To avoid exposing patients to unnecessary treatments, it is critical for clinicians to recognize that comorbid pulmonary conditions may mimic metastatic PTC on radioiodine scintigraphy.

Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

International Nuclear Information System (INIS)

Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J.

2016-01-01

Ozone (O 3 )-related cardiorespiratory effects are a growing public health concern. Ground level O 3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O 3 -induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O 3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O 3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O 2 ) or hypoxia (10.0% O 2 ), followed by a 4-h exposure to either 1 ppm O 3 or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O 3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O 3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O 3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O 3 -induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive pulmonary disease (COPD). • It is unknown if comorbid

Line-Enhanced Deformable Registration of Pulmonary Computed Tomography Images Before and After Radiation Therapy With Radiation-Induced Fibrosis

Science.gov (United States)

Sensakovic, William F.; Maxim, Peter; Diehn, Maximilian; Loo, Billy W.; Xing, Lei

2018-01-01

Purpose: The deformable registration of pulmonary computed tomography images before and after radiation therapy is challenging due to anatomic changes from radiation fibrosis. We hypothesize that a line-enhanced registration algorithm can reduce landmark error over the entire lung, including the irradiated regions, when compared to an intensity-based deformable registration algorithm. Materials: Two intensity-based B-spline deformable registration algorithms of pre-radiation therapy and post-radiation therapy images were compared. The first was a control intensity–based algorithm that utilized computed tomography images without modification. The second was a line enhancement algorithm that incorporated a Hessian-based line enhancement filter prior to deformable image registration. Registrations were evaluated based on the landmark error between user-identified landmark pairs and the overlap ratio. Results: Twenty-one patients with pre-radiation therapy and post-radiation therapy scans were included. The median time interval between scans was 1.2 years (range: 0.3-3.3 years). Median landmark errors for the line enhancement algorithm were significantly lower than those for the control algorithm over the entire lung (1.67 vs 1.83 mm; P 5 Gy (2.25 vs 3.31; P 5 Gy dose interval demonstrated a significant inverse relationship with post-radiation therapy fibrosis enhancement after line enhancement filtration (Pearson correlation coefficient = −0.48; P = .03). Conclusion: The line enhancement registration algorithm is a promising method for registering images before and after radiation therapy. PMID:29343206

Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.

Science.gov (United States)

Babu, K Anand; Supraja, K; Singh, Raj B

2014-01-01

Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

[EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

Science.gov (United States)

Shostak, Yael; Kramer, Mordechai R

2017-11-01

Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.

Science.gov (United States)

Li, Ji-Feng; Zhai, Zhen-Guo; Kuang, Tu-Guang; Liu, Min; Ma, Zhan-Hong; Li, Yi-Dan; Yang, Yuan-Hua

2017-08-01

Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice

NARCIS (Netherlands)

Reed, JA; Ikegami, M; Robb, L; Begley, CG; Ross, G; Whitsett, JA

Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GMCSF) or GM receptor common beta-chain (beta(c)) genes in mice [GM(-/-), beta(c)(-/-)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To

Pulmonary langerhans cell histiocytosis

Directory of Open Access Journals (Sweden)

Suri Harpreet S

2012-03-01

Full Text Available Abstract Pulmonary Langerhans Cell Histiocytosis (PLCH is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

Science.gov (United States)

López Gude, María Jesús; Pérez de la Sota, Enrique; Pérez Vela, Jose Luís; Centeno Rodríguez, Jorge; Muñoz Guijosa, Christian; Velázquez, María Teresa; Alonso Chaterina, Sergio; Hernández González, Ignacio; Escribano Subías, Pilar; Cortina Romero, José María

2017-07-07

Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm -5 , and group 2, which included the remaining 120 patients. Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.

Science.gov (United States)

Gao, Zhenxing; Zhang, Huixia; Hu, Fei; Yang, Liheng; Yang, Xiaowen; Zhu, Ying; Sy, Man-Sun; Li, Chaoyang

2016-06-01

Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Lysyl Oxidase-Like 1 Protein Deficiency Protects Mice from Adenoviral Transforming Growth Factor-β1-induced Pulmonary Fibrosis.

Science.gov (United States)

Bellaye, Pierre-Simon; Shimbori, Chiko; Upagupta, Chandak; Sato, Seidai; Shi, Wei; Gauldie, Jack; Ask, Kjetil; Kolb, Martin

2018-04-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue, disturbing gas exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of transforming growth factor (TGF)-β1, one of the main profibrotic growth factors. Lysyl oxidase-like (LOXL) 1 belongs to the cross-linking enzyme family and has been shown to be up-regulated in active fibrotic regions of bleomycin-treated mice and patients with IPF. We demonstrate in this study that LOXL1-deficient mice are protected from experimental lung fibrosis induced by overexpression of TGF-β1 using adenoviral (Ad) gene transfer (AdTGF-β1). The lack of LOXL1 prevented accumulation of insoluble cross-linked collagen in the lungs, and therefore limited lung stiffness after AdTGF-β1. In addition, we applied mechanical stretch to lung slices from LOXL1 +/+ and LOXL1 -/- mice treated with AdTGF-β1. Lung stiffness (Young's modulus) of LOXL1 -/- lung slices was significantly lower compared with LOXL1 +/+ lung slices. Moreover, the release of activated TGF-β1 after mechanical stretch was significantly lower in LOXL1 -/- mice compared with LOXL1 +/+ mice after AdTGF-β1. These data support the concept that cross-linking enzyme inhibition represents an interesting therapeutic target for drug development in IPF.

Modulation of inflammasome-mediated pulmonary immune activation by type I IFNs protects bone marrow homeostasis during systemic responses to Pneumocystis lung infection.

Science.gov (United States)

Searles, Steve; Gauss, Katherine; Wilkison, Michelle; Hoyt, Teri R; Dobrinen, Erin; Meissner, Nicole

2013-10-01

Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, possible innate immune defects as a cause for systemic immune deviations in response to otherwise innocuous infections have not been extensively explored. In this regard, we recently demonstrated an important role of type I IFNs in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice deficient in both lymphocytes and type I IFN receptor (IFrag(-/-) mice) develop rapidly progressing BMF due to accelerated bone marrow (BM) cell apoptosis associated with innate immune deviations in the BM in response to Pneumocystis lung infection. However, the communication pathway between lung and BM eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. In this study, we report that absence of an intact type I IFN system during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient mice but also transient BM stress in lymphocyte-competent mice. This is associated with an exuberant systemic IFN-γ response. IFN-γ neutralization prevented Pneumocystis lung infection-induced BM depression in type I IFN receptor-deficient mice and prolonged neutrophil survival time in BM from IFrag(-/-) mice. IL-1β and upstream regulators of IFN-γ, IL-12, and IL-18 were also upregulated in lung and serum of IFrag(-/-) mice. In conjunction, there was exuberant inflammasome-mediated caspase-1 activation in pulmonary innate immune cells required for processing of IL-18 and IL-1β. Thus, absence of type I IFN signaling during Pneumocystis lung infection may result in deregulation of inflammasome-mediated pulmonary immune activation, causing systemic immune deviations triggering BMF in this model.

Enhancement of lipid production in two marine microalgae under different levels of nitrogen and phosphorus deficiency.

Science.gov (United States)

Adenan, Nurul Salma; Yusoff, Fatimah Md; Medipally, Srikanth Reddy; Shariff, M

2016-07-01

Microalgae are important food sources for aquaculture animals. Among the different factors which influence the biochemical composition of microalgae, nitrogen and phosphorus are two of the most important nutrient sources for growth and development. The present study aimed to assess the effects of nitrogen and phosphorus deficiency on lipid production of Chlorella sp. and Chaetoceros calcitrans. Early stationary phase culture of these species were exposed to different stress levels of nitrogen and phosphorus (25%, 50% and 75% of the full NO(3)-N and PO(4)-P concentration in the Conway media), and solvent extraction and gas-liquid chromatography methods were performed for analysis of lipid and fatty acid composition. The results revealed that lipid production in these two species significantly increased (Pnitrogen and phosphorus decreased. The fatty acid proportion remained unaffected under nitrogen deficiency, while phosphorus limitation resulted in a decrease of saturated fatty acids and promoted a higher content of omega-3 fatty acids in these species. The protein and carbohydrate levels were also altered under limited nutrients. Therefore, these conditions could be used for enhanced lipid production in microalgae for aquaculture and other industrial applications.

Lack of bleeding in patients with severe factor VII deficiency.

Science.gov (United States)

Barnett, J Mark; Demel, Kurt C; Mega, Anthony E; Butera, James N; Sweeney, Joseph D

2005-02-01

Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Copyright 2005 Wiley-Liss, Inc.

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi

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Clark Tamara D

2004-12-01

Full Text Available Abstract Background Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV load in adults with pulmonary tuberculosis. Methods In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. Results Body mass index (BMI, plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations Conclusions These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

The role of receptor-mediated T-cells activation disorders in pulmonary tuberculosis

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Irina E. Esimova

2017-01-01

Full Text Available Aim. To analyze the peculiarities and mechanisms of receptor-mediated T-lymphocytes disorders in different clinical forms of pulmonary tuberculosis.Materials and мethods. The study involved 116 patients with first diagnosed infiltrative and disseminated drug-sensitive and drug-resistant pulmonary tuberculosis. The key stages in receptor-mediated activation of T-lymphocytes, isolated from blood, after their CD3/CD28-induction in vitro with addition of intracellular transport blocker were analyzed. Their immunotyping was carried out with the method of two- and threecolor flow cytofluorometry. The obtained results were statistically analyzed.Results. The breach of extracellular and intracellular stages of T-lymphocytes activation, shown by reduction in total number of CD3- and CD28-positive cells, and CD3+CD28+IL2+, CD3+CD28+IL2–, CD3+NF-kB+, CD3+NFAT2+ lymphocytes, and increase in number of CD3+CTLA4+ cells, was identified with most of their manifestations in disseminated drug-resistant pulmonary tuberculosis. It was shown that the content of CD3+AP-1+ lymphocytes is variable in drug-resistant pulmonary tuberculosis: it increases in the infiltrative form and decreases in the disseminated form.Conclusion. The results showed different mechanisms leading to a deficiency of IL-2-positive lymphocytes and T-lymphocytopenia: from “functional reserve” exhaustion of T-cells in drug-sensitive pulmonary tuberculosis to immunosuppression under the influence of suppressive cytokines (in case of the infiltrative form and inhibitory protein CTLA4 (in case of the disseminated form in drug-resistant pulmonary tuberculosis. 

Partial anomalous pulmonary venous return in patients with pulmonary hypertension

International Nuclear Information System (INIS)

Sung, Won-kyung; Au, Virginia; Rose, Anand

2012-01-01

Anomalous pulmonary venous return is an uncommon congenital malformation, and may be partial or total. Partial anomalous pulmonary venous return (PAPVR) is more common than total anomalous pulmonary venous return, and is often associated with other congenital cardiac anomalies. Whilst many patients with PAPVR remain asymptomatic, some may present in later age with symptoms related to left-to-right shunt, right heart failure and pulmonary hypertension. We report two cases of PAPVR detected on Computed Tomography Pulmonary Angiogram (CTPA) for the work up of pulmonary hypertension. The cases demonstrate that, although uncommon, partial anomalous pulmonary venous return can be a contributing factor to pulmonary hypertension and pulmonary veins should be carefully examined when reading a CTPA study.

Eisenmenger syndrome and idiopathic pulmonary arterial hypertension: do parenchymal lung changes reflect aetiology?

International Nuclear Information System (INIS)

Griffin, N.; Allen, D.; Wort, J.; Rubens, M.; Padley, S.

2007-01-01

Aim: To document the pulmonary vascular changes on thin-section computed tomography (CT) in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension, and to determine whether there is any correlation with pulmonary arterial pressures or the aetiology of pulmonary hypertension. Material and methods: From the National Pulmonary Hypertension Database, we identified eight patients with idiopathic pulmonary arterial hypertension and 20 patients with Eisenmenger syndrome (secondary to a ventriculoseptal defect) who had also undergone contrast-enhanced thin-section CT. CT studies were reviewed for the presence of centrilobular nodules, mosaicism, neovascularity, and bronchial artery hypertrophy. Haemodynamic data were also reviewed. Results: Centrilobular nodules, mosaicism, and neovascularity were seen in both patient groups (p > 0.05). A significantly higher number of enlarged bronchial arteries were seen in patients with Eisenmenger syndrome. There was no correlation with pulmonary arterial pressures. Conclusion: Patients with idiopathic pulmonary arterial hypertension and Eisenmenger syndrome demonstrated similar pulmonary vascular changes on CT. These changes did not predict the underlying cause of pulmonary hypertension or its severity

Eisenmenger syndrome and idiopathic pulmonary arterial hypertension: do parenchymal lung changes reflect aetiology?

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Griffin, N. [Royal Brompton and Harefield NHS Trust, London (United Kingdom)]. E-mail: nyreegriffin@hotmail.com; Allen, D. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Wort, J. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Rubens, M. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Padley, S. [Royal Brompton and Harefield NHS Trust, London (United Kingdom)

2007-06-15

Aim: To document the pulmonary vascular changes on thin-section computed tomography (CT) in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension, and to determine whether there is any correlation with pulmonary arterial pressures or the aetiology of pulmonary hypertension. Material and methods: From the National Pulmonary Hypertension Database, we identified eight patients with idiopathic pulmonary arterial hypertension and 20 patients with Eisenmenger syndrome (secondary to a ventriculoseptal defect) who had also undergone contrast-enhanced thin-section CT. CT studies were reviewed for the presence of centrilobular nodules, mosaicism, neovascularity, and bronchial artery hypertrophy. Haemodynamic data were also reviewed. Results: Centrilobular nodules, mosaicism, and neovascularity were seen in both patient groups (p > 0.05). A significantly higher number of enlarged bronchial arteries were seen in patients with Eisenmenger syndrome. There was no correlation with pulmonary arterial pressures. Conclusion: Patients with idiopathic pulmonary arterial hypertension and Eisenmenger syndrome demonstrated similar pulmonary vascular changes on CT. These changes did not predict the underlying cause of pulmonary hypertension or its severity.

Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

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Ken-Ichiro Inoue

2011-01-01

Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

CT diagnosis of primary lung cancer coexisting with pulmonary tuberculosis

International Nuclear Information System (INIS)

Kim, Sun Joo; Kim, Young Sook; Oh, Jae Hee; Kim, Eun Kyoung; Kim, Young Chul

1992-01-01

When bronchogenic carcinoma is coexisting with pulmonary tuberculosis, it is difficult to differentiate bronchogenic carcinoma from pulmonary tuberculosis radiographically. Thus, the object of this study is to define differential diagnosis of bronchogenic carcinoma by computed tomography. We analyzed CT scans of 27 patients with radiologic findings of pulmonary tuberculosis and mass of which twelve cases were pulmonary tuberculosis and fifteen cases were primary lung cancer. The location of parenchymal infiltration and the mass was the same in 60%(9/15) of the primary lung cancer in cases and 83%(10/12) of the pulmonary tuberculosis cases. The common location of the mass was the both upper lobes in 92%(11/12) of the pulmonary tuberculosis cases and 53%(8/15) of the primary lung cancer cases. The common locations of the mediastinal lymphadenopathy were 4R, 2R of the pulmonary tuberculosis cases and 4R, 10R of the primary lung cancer cases. In the feature of post enhanced lymph nodes, homogenous increased density was more frequent in primary lung cancer. Measurements of the maximum thickness part of the cavity wall was not a reliable indication of malignancy

Pulmonary biomarkers in chronic obstructive pulmonary disease

NARCIS (Netherlands)

Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina

2006-01-01

There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current

Evaluation of 16 detector row spiral CT in diagnosing pulmonary embolism

International Nuclear Information System (INIS)

Yu Xiaokun; Li Lei

2008-01-01

Objective: To investigate the value of 16 detector row spiral CT in the diagnosis of pulmonary embolism(PE). Methods: Imaging data of 20 patients (plain 16 detector row spiral CT scanning plus enhanced scanning imaging) highly suspected of PE was retrospectively analyzed. Results: Among the 20 cases, embolism was showed in 13 patients on 16 detector row spiral CT pulmonary angiography (MSCTPA). 6 cases of the 13 PE's patients have masculine findings on plain MSCT scanning images. Localized tenuous lung markings, dilated pulmonary artery, 'mosaic' sign, pleural or pericardial effusion, local high attenuation centrally in the pulmonary arteries and lung infarction occurred respectively. Conclusion: MSCTPA may be an effective, simple and safe technique for the diagnosis of PE. It was a reliable means in defecting PE However, for the cases unfit for contrast media and cases only suitable for unenhanced CT because of nonspecific heart-pulmonary symptom, noticeable abnormal signs of plain MSCT scanning could suggest the occurrence of pulmonary embolism. (authors)

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.

Science.gov (United States)

Hollak, C E M; de Sonnaville, E S V; Cassiman, D; Linthorst, G E; Groener, J E; Morava, E; Wevers, R A; Mannens, M; Aerts, J M F G; Meersseman, W; Akkerman, E; Niezen-Koning, K E; Mulder, M F; Visser, G; Wijburg, F A; Lefeber, D; Poorthuis, B J H M

2012-11-01

Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone

Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic pulmonary arterial hypertension

DEFF Research Database (Denmark)

Andersen, Kasper Hasseriis; Andersen, Claus Bøgelund; Gustafsson, Finn

2017-01-01

Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive...... pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH......) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic...

Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

International Nuclear Information System (INIS)

Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

1984-01-01

The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries

When a pulmonary embolism is not a pulmonary embolism: a rare case of primary pulmonary leiomyosarcoma

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Nargiz Muganlinskaya

2015-12-01

Full Text Available Arterial leiomyosarcomas account for up to 21% of vascular leiomyosarcomas, with 56% of arterial leiomyosarcomas occurring in the pulmonary artery. While isolated cases of primary pulmonary artery leiomyosarcoma document survival up to 36 months after treatment, these uncommon, aggressive tumors are highly lethal, with 1-year survival estimated at 20% from the onset of symptoms. We discuss a rare case of a pulmonary artery leiomyosarcoma that was originally diagnosed as a pulmonary embolism (PE. A 72-year-old Caucasian female was initially diagnosed with ‘saddle pulmonary embolism’ based on computerized tomographic angiography of the chest 2 months prior to admission and placed on anticoagulation. Dyspnea escalated, and serial computed tomography scans showed cardiomegaly with pulmonary emboli involving the right and left main pulmonary arteries with extension into the right and left upper and lower lobe branches. An echocardiogram on admission showed severe pulmonary hypertension with a pulmonary artery pressure of 82.9 mm Hg, and a severely enlarged right ventricle. Respiratory distress and multiorgan failure developed and, unfortunately, the patient expired. Autopsy showed a lobulated, yellow mass throughout the main pulmonary arteries measuring 13 cm in diameter. The mass extended into the parenchyma of the right upper lobe. On microscopy, the mass was consistent with a high-grade primary pulmonary artery leiomyosarcoma. Median survival of patients with primary pulmonary artery leiomyosarcoma without surgery is one and a half months, and mortality is usually due to right-sided heart failure. Pulmonary artery leiomyosarcoma is a rare but highly lethal disease commonly mistaken for PE. Thus, we recommend clinicians to suspect this malignancy when anticoagulation fails to relieve initial symptoms. In conclusion, early detection and suspicion of pulmonary artery leiomyosarcoma should be considered in patients refractory to anticoagulation

An ROC study detecting ability of idiopathic pulmonary fibrosis using digital radiography

International Nuclear Information System (INIS)

Chung, Eun Chul; Im, Jung Gi; Han, Man Chung; Kim, Jong Hyo

1991-01-01

One potential advantage of the digital radiography system is its ability to enhance image quality by various types of processing. Digital unsharp masking is one of the simplest and most useful forms of enhancing processes. The efficacy of unsharp masking in radiological diagnosis has not been investigated thoroughly. To evaluate the effects of unsharp masking in film-digital chest images, 3 observers were shown 150 test radiographs. These test radiographs consisted of 50 unprocessed images (25 normals and 25 patients with idiopathic pulmonary fibrosis with honey combing) and their 100 processed images by using 450 and 15-sized masks respectively. An ROC analysis of these data suggests that unsharp masking is more effective in detecting idiopathic pulmonary fibrosis than unprocessed image (ρ < 0.05), and so it may improve diagnostic accuracy for interstitial fibrosis. In addition, the smaller mask size (15) is more effective than the larger one (mask size 45) (ρ < 0.05). By using this analytic approach, an optimal parameter in digital chest radiography may be investigated in many other forms of pulmonary disease such as pulmonary nodule or mediastinal mass

An ROC study detecting ability of idiopathic pulmonary fibrosis using digital radiography

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Chung, Eun Chul; Im, Jung Gi; Han, Man Chung; Kim, Jong Hyo [College of Medicine, Ewha Womens University, Seoul (Korea, Republic of)

1991-03-15

One potential advantage of the digital radiography system is its ability to enhance image quality by various types of processing. Digital unsharp masking is one of the simplest and most useful forms of enhancing processes. The efficacy of unsharp masking in radiological diagnosis has not been investigated thoroughly. To evaluate the effects of unsharp masking in film-digital chest images, 3 observers were shown 150 test radiographs. These test radiographs consisted of 50 unprocessed images (25 normals and 25 patients with idiopathic pulmonary fibrosis with honey combing) and their 100 processed images by using 450 and 15-sized masks respectively. An ROC analysis of these data suggests that unsharp masking is more effective in detecting idiopathic pulmonary fibrosis than unprocessed image ({rho} < 0.05), and so it may improve diagnostic accuracy for interstitial fibrosis. In addition, the smaller mask size (15) is more effective than the larger one (mask size 45) ({rho} < 0.05). By using this analytic approach, an optimal parameter in digital chest radiography may be investigated in many other forms of pulmonary disease such as pulmonary nodule or mediastinal mass.

Pulmonary histiocytosis X - imaging aspects of pulmonary involvement

International Nuclear Information System (INIS)

Sabedotti, Ismail Fernando; Maeda, Lucimara; Ferreira, Daniel Miranda; Montandon, Cristiano; Marins, Jose Luiz C.

1999-01-01

Pulmonary histiocytosis X is an idiopathic disease which is and uncommon but important cause of pulmonary fibrosis in young adults. Chest radiographs and high resolution computed tomographic (HRCT) scans of the lungs of 7 patients diagnosed as pulmonary histiocytosis X were examined retrospectively. The authors reviewed the pathologic, clinical and radiographic features of pulmonary histiocytosis X, focusing on differential diagnosis and disease progression. Pulmonary histiocytosis X can be suspected on the basis of chest radiographic findings; predominantly upper lobe nodules and cysts present an increased sensitivity and are virtually pathognomonic of this disorder. Chest HRCT allows good assessment of the evolution of pulmonary histiocytosis X and is also valuable in distinguishing histiocytosis from other disorders that produces nodules or cysts. (author)

Pulmonary arteriography by digital subtraction angiographic method in cyanotic heart disease with pulmonary stenosis or pulmonary atresia

International Nuclear Information System (INIS)

Kobayashi, Junjiro; Hirose, Hajime; Nakano, Susumu

1985-01-01

Pulmonary arteriography was performed by digital subtraction angiographic (DSA) method in 10 patients with cyanotic heart disease associated with pulmonary stenosis or pulmonary atresia. Ten patients consisted of five patients with tetralogy of Fallot, three with single ventricle and pulmonary stenosis, and two with pseudotruncus arteriosus. Hepato-clavicular position was taken in four patients. Pulmonary artery and its main branches were opacified and recognized clearly, and their diameter could be measured accurately with a small amount of contrast medium. There was a good correlation between the diameter of pulmonary artery measured by DSA and that measured by conventional pulmonary arteriography. DSA is a useful method for evaluating the size and the stenosis of pulmonary artery especially in small cyanotic infants. (author)

Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

Energy Technology Data Exchange (ETDEWEB)

Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J., E-mail: mcampen@salud.unm.edu

2016-08-15

Ozone (O{sub 3})-related cardiorespiratory effects are a growing public health concern. Ground level O{sub 3} can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O{sub 3}-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O{sub 3} pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O{sub 3} exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O{sub 2}) or hypoxia (10.0% O{sub 2}), followed by a 4-h exposure to either 1 ppm O{sub 3} or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O{sub 3} exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O{sub 3} exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O{sub 3} exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O{sub 3}-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive

Computerized axial tomography of the chest for visualization of ''absent'' pulmonary arteries

Energy Technology Data Exchange (ETDEWEB)

Sondheimer, H.M. (Upstate Medical Center, Syracuse, NY); Oliphant, M.; Schneider, B.; Kavey, R.E.W.; Blackman, M.S.; Parker, F.B. Jr.

1982-05-01

To expand the search for central pulmonary arteries in six patients with absence of cardiac-pulmonary continuity, computerized axial tomography (CAT) of the chest was performed. The CAT scans were compared with previous arteriograms and pulmonary vein wedge angiograms. Three patients with type IV truncus arteriosus were studied, and none had a central, right or left pulmonary artery on CAT scan. However, two patients with tetralogy of Fallot with pulmonary atresia and a patent ductus arteriosus to the right lung demonstrated the presence of a left pulmonary artery. In addition, one child with truncus arteriosus with ''absent'' left pulmonary artery demonstrated a left pulmonary artery on the CAT scan. The CAT scan may therefore enhance our ability to search for disconnected pulmonary arteries in children with complex cyanotic congenital heart disease.

The change of longitudinal relaxation rate in oxygen enhanced pulmonary MRI depends on age and BMI but not diffusing capacity of carbon monoxide in healthy never-smokers.

Directory of Open Access Journals (Sweden)

Simon Sven Ivan Kindvall

Full Text Available Oxygen enhanced pulmonary MRI is a promising modality for functional lung studies and has been applied to a wide range of pulmonary conditions. The purpose of this study was to characterize the oxygen enhancement effect in the lungs of healthy, never-smokers, in light of a previously established relationship between oxygen enhancement and diffusing capacity of carbon monoxide in the lung (DL,CO in patients with lung disease.In 30 healthy never-smoking volunteers, an inversion recovery with gradient echo read-out (Snapshot-FLASH was used to quantify the difference in longitudinal relaxation rate, while breathing air and 100% oxygen, ΔR1, at 1.5 Tesla. Measurements were performed under multiple tidal inspiration breath-holds.In single parameter linear models, ΔR1 exhibit a significant correlation with age (p = 0.003 and BMI (p = 0.0004, but not DL,CO (p = 0.33. Stepwise linear regression of ΔR1 yields an optimized model including an age-BMI interaction term.In this healthy, never-smoking cohort, age and BMI are both predictors of the change in MRI longitudinal relaxation rate when breathing oxygen. However, DL,CO does not show a significant correlation with the oxygen enhancement. This is possibly because oxygen transfer in the lung is not diffusion limited at rest in healthy individuals. This work stresses the importance of using a physiological model to understand results from oxygen enhanced MRI.

Interleukin-6 overexpression induces pulmonary hypertension.

Science.gov (United States)

Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

2009-01-30

Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

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Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

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Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

2017-01-01

Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

Pulmonary capillary pressure in pulmonary hypertension.

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Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

2005-04-01

Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

Fractal Dimension Analysis of MDCT Images for Quantifying the Morphological Changes of the Pulmonary Artery Tree in Patients with Pulmonary Hypertension

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Sun, Haitao; Li, Ning; Guo, Lijun; Gao, Fei; Liu, Cheng [Shandong University, Shandong Medical Imaging Research Institute, Shandong (Korea, Republic of)

2011-06-15

The aim of this study was to use fractal dimension (FD) analysis on multidetector CT (MDCT) images for quantifying the morphological changes of the pulmonary artery tree in patients with pulmonary hypertension (PH). Fourteen patients with PH and 17 patients without PH as controls were studied. All of the patients underwent contrast-enhanced helical CT and transthoracic echocardiography. The pulmonary artery trees were generated using post-processing software, and the FD and projected image area of the pulmonary artery trees were determined with Image J software in a personal computer. The FD, the projected image area and the pulmonary artery pressure (PAP) were statistically evaluated in the two groups. The FD, the projected image area and the PAP of the patients with PH were higher than those values of the patients without PH (p < 0.05, t-test). There was a high correlation of FD with the PAP (r = 0.82, p < 0.05, partial correlation analysis). There was a moderate correlation of FD with the projected image area (r = 0.49, p < 0.05, partial correlation analysis). There was a correlation of the PAP with the projected image area (r = 0.65, p < 0.05, Pearson correlation analysis). The FD of the pulmonary arteries in the PH patients was significantly higher than that of the controls. There is a high correlation of FD with the PAP.

Fractal Dimension Analysis of MDCT Images for Quantifying the Morphological Changes of the Pulmonary Artery Tree in Patients with Pulmonary Hypertension

International Nuclear Information System (INIS)

Sun, Haitao; Li, Ning; Guo, Lijun; Gao, Fei; Liu, Cheng

2011-01-01

The aim of this study was to use fractal dimension (FD) analysis on multidetector CT (MDCT) images for quantifying the morphological changes of the pulmonary artery tree in patients with pulmonary hypertension (PH). Fourteen patients with PH and 17 patients without PH as controls were studied. All of the patients underwent contrast-enhanced helical CT and transthoracic echocardiography. The pulmonary artery trees were generated using post-processing software, and the FD and projected image area of the pulmonary artery trees were determined with Image J software in a personal computer. The FD, the projected image area and the pulmonary artery pressure (PAP) were statistically evaluated in the two groups. The FD, the projected image area and the PAP of the patients with PH were higher than those values of the patients without PH (p < 0.05, t-test). There was a high correlation of FD with the PAP (r = 0.82, p < 0.05, partial correlation analysis). There was a moderate correlation of FD with the projected image area (r = 0.49, p < 0.05, partial correlation analysis). There was a correlation of the PAP with the projected image area (r = 0.65, p < 0.05, Pearson correlation analysis). The FD of the pulmonary arteries in the PH patients was significantly higher than that of the controls. There is a high correlation of FD with the PAP.

Pulmonary edema

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... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension.

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Juratsch, C E; Grover, R F; Rose, C E; Reeves, J T; Walby, W F; Laks, M M

1985-04-01

Distension of the main pulmonary artery (MPA) induces pulmonary hypertension, most probably by neurogenic reflex pulmonary vasoconstriction, although constriction of the pulmonary vessels has not actually been demonstrated. In previous studies in dogs with increased pulmonary vascular resistance produced by airway hypoxia, exogenous arachidonic acid has led to the production of pulmonary vasodilator prostaglandins. Hence, in the present study, we investigated the effect of arachidonic acid in seven intact anesthetized dogs after pulmonary vascular resistance was increased by MPA distention. After steady-state pulmonary hypertension was established, arachidonic acid (1.0 mg/min) was infused into the right ventricle for 16 min; 15-20 min later a 16-mg bolus of arachidonic acid was injected. MPA distension was maintained throughout the study. Although the infusion of arachidonic acid significantly lowered the elevated pulmonary vascular resistance induced by MPA distension, the pulmonary vascular resistance returned to control levels only after the bolus injection of arachidonic acid. Notably, the bolus injection caused a biphasic response which first increased the pulmonary vascular resistance transiently before lowering it to control levels. In dogs with resting levels of pulmonary vascular resistance, administration of arachidonic acid in the same manner did not alter the pulmonary vascular resistance. It is concluded that MPA distension does indeed cause reflex pulmonary vasoconstriction which can be reversed by vasodilator metabolites of arachidonic acid. Even though this reflex may help maintain high pulmonary vascular resistance in the fetus, its function in the adult is obscure.

Solitary pulmonary nodules: Comparison of dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic first-pass contrast-enhanced MR imaging, and FDG PET/CT.

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Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Seki, Shinichiro; Tsubakimoto, Maho; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2015-02-01

To prospectively compare the capabilities of dynamic perfusion area-detector computed tomography (CT), dynamic magnetic resonance (MR) imaging, and positron emission tomography (PET) combined with CT (PET/CT) with use of fluorine 18 fluorodeoxyglucose (FDG) for the diagnosis of solitary pulmonary nodules. The institutional review board approved this study, and written informed consent was obtained from each subject. A total of 198 consecutive patients with 218 nodules prospectively underwent dynamic perfusion area-detector CT, dynamic MR imaging, FDG PET/CT, and microbacterial and/or pathologic examinations. Nodules were classified into three groups: malignant nodules (n = 133) and benign nodules with low (n = 53) or high (n = 32) biologic activity. Total perfusion was determined with dual-input maximum slope models at area-detector CT, maximum and slope of enhancement ratio at MR imaging, and maximum standardized uptake value (SUVmax) at PET/CT. Next, all indexes for malignant and benign nodules were compared with the Tukey honest significant difference test. Then, receiver operating characteristic analysis was performed for each index. Finally, sensitivity, specificity, and accuracy were compared with the McNemar test. All indexes showed significant differences between malignant nodules and benign nodules with low biologic activity (P Dynamic perfusion area-detector CT is more specific and accurate than dynamic MR imaging and FDG PET/CT in the diagnosis of solitary pulmonary nodules in routine clinical practice. © RSNA, 2014.

CD44 deficiency enhanced Streptococcus equi ssp. zooepidemicus dissemination and inflammation response in a mouse model.

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Fu, Qiang; Xiao, Pingping; Chen, Yaosheng; Wei, Zigong; Liu, Xiaohong

2017-12-01

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased. CD44 deficiency accelerated mortality, which was accompanied by increased peritoneal bacterial growth and dissemination to distant body sites. CD44 knock-out (KO) mice showed enhanced early inflammatory cell recruitment into the peritoneal fluid on S. zooepidemicus infection. In line with this, the expression of proinflammatory cytokines, chemokines in peritoneal exudate cells and peritoneal macrophages of CD44 KO mice were increased compared with those of WT mice. In addition, CD44 deficiency was associated with reduced expression of A20, a negative regulator in TLR signaling. Overall, the present study suggests that CD44 plays a protective role in antibacterial defense against S. zooepidemicus in mice. Copyright © 2017. Published by Elsevier Ltd.

Pulmonary tuberculosis

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TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

Peripheral pulmonary arteries: identification at multi-slice spiral CT with 3D reconstruction

International Nuclear Information System (INIS)

Coche, Emmanuel; Pawlak, Sebastien; Dechambre, Stephane; Maldague, Baudouin

2003-01-01

Our objective was to analyze the peripheral pulmonary arteries using thin-collimation multi-slice spiral CT. Twenty consecutive patients underwent enhanced-spiral multi-slice CT using 1-mm collimation. Two observers analyzed the pulmonary arteries by consensus on a workstation. Each artery was identified on axial and 3D shaded-surface display reconstruction images. Each subsegmental artery was measured at a mediastinal window setting and compared with anatomical classifications. The location and branching of every subsegmental artery was recorded. The number of well-visualized sub-subsegmental arteries at a mediastinal window setting was compared with those visualized at a lung window setting. Of 800 subsegmental arteries, 769 (96%) were correctly visualized and 123 accessory subsegmental arteries were identified using the mediastinal window setting. One thousand ninety-two of 2019 sub-subsegmental arteries (54%) identified using the lung window setting were correctly visualized using the mediastinal window setting. Enhanced multi-slice spiral CT with thin collimation can be used to analyze precisely the subsegmental pulmonary arteries and may identify even more distal pulmonary arteries. (orig.)

Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis.

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Kannengiesser, Caroline; Borie, Raphael; Ménard, Christelle; Réocreux, Marion; Nitschké, Patrick; Gazal, Steven; Mal, Hervé; Taillé, Camille; Cadranel, Jacques; Nunes, Hilario; Valeyre, Dominique; Cordier, Jean François; Callebaut, Isabelle; Boileau, Catherine; Cottin, Vincent; Grandchamp, Bernard; Revy, Patrick; Crestani, Bruno

2015-08-01

Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. Defective telomere maintenance leading to telomere shortening is a cause of pulmonary fibrosis, as mutations in the telomerase component genes TERT (reverse transcriptase) and TERC (RNA component) are found in 15% of familial pulmonary fibrosis (FPF) cases. However, so far, about 85% of FPF remain genetically uncharacterised.Here, in order to identify new genetic causes of FPF, we performed whole-exome sequencing, with a candidate-gene approach, of 47 affected subjects from 35 families with FPF without TERT and TERC mutations.We identified heterozygous mutations in regulator of telomere elongation helicase 1 (RTEL1) in four families. RTEL1 is a DNA helicase with roles in DNA replication, genome stability, DNA repair and telomere maintenance. The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, and were predicted by structural analyses to severely affect the function and/or stability of RTEL1. In agreement with this, RTEL1-mutated patients exhibited short telomeres in comparison with age-matched controls.Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby, extend the clinical spectrum of RTEL1 deficiency. Thus, RTEL1 enlarges the number of telomere-associated genes implicated in FPF. Copyright ©ERS 2015.

Enhanced thermoelectric properties of N-type polycrystalline In4Se3-x compounds via thermally induced Se deficiency

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Zhao, Ran; Shu, Yu-Tian; Guo, Fu

2014-03-01

In4Se3-x compound is considered as a potential thermoelectric material due to its comparably low thermal conductivity among all existing ones. While most studies investigated In4Se3-x thermoelectric properties by controlling selennium or other dopants concentrations, in the current study, it was found that even for a fixed initial In/Se ratio, the resulting In/Se ratio varied significantly with different thermal processing histories (i.e., melting and annealing), which also resulted in varied thermoelectric properties as well as fracture surface morphologies of In4Se3-x polycrystalline specimens. Single phase polycrystalline In4Se3-x compounds were synthesized by combining a sequence of melting, annealing, pulverizing, and spark plasma sintering. The extension of previous thermal history was observed to significantly improve the electrical conductivity (about 121%) and figure of merit (about 53%) of In4Se3-x polycrystalline compounds. The extended thermal history resulted in the increase of Se deficiency (x) from 0.39 to 0.53. This thermally induced Se deficiency was observed to associate with increasing carrier mobility but decreasing concentration, which differs from the general trend observed for the initially adjusted Se deficiency at room temperature. Unusually large dispersed grains with nanosize layers were observed in specimens with the longest thermal history. The mechanism(s) by which previous thermal processing enhances carrier mobility and affect microstructural evolution are briefly discussed.

Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: New Horizons in the Interventional Management of Pulmonary Embolism.

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Rivers-Bowerman, Michael D; Zener, Rebecca; Jaberi, Arash; de Perrot, Marc; Granton, John; Moriarty, John M; Tan, Kong T

2017-09-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed potential complication of acute or recurrent pulmonary thromboembolic disease. Multiple studies suggest that up to 5% of patients with acute pulmonary thromboembolic disease go on to develop CTEPH. The prognosis of untreated CTEPH is poor, but advances in medical and surgical treatments over the past few decades have improved patient outcomes. The gold standard and curative treatment for CTEPH is pulmonary endarterectomy; however, some patients are inoperable and others who have undergone pulmonary endarterectomy experience persistent or recurrent pulmonary hypertension despite medical therapy. In recent years, balloon pulmonary angioplasty has emerged as a primary and adjunctive treatment for these CTEPH patients at expert or specialized centers. This review outlines an approach to balloon pulmonary angioplasty for CTEPH, including clinical presentation and evaluation; patient selection and indications; treatment planning; equipment and technique; overcoming technical challenges; recognition and management of complications; postprocedural care and clinical follow-up; and expected outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension.

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El Kasmi, Karim C; Pugliese, Steven C; Riddle, Suzette R; Poth, Jens M; Anderson, Aimee L; Frid, Maria G; Li, Min; Pullamsetti, Soni S; Savai, Rajkumar; Nagel, Maria A; Fini, Mehdi A; Graham, Brian B; Tuder, Rubin M; Friedman, Jacob E; Eltzschig, Holger K; Sokol, Ronald J; Stenmark, Kurt R

2014-07-15

Macrophage accumulation is not only a characteristic hallmark but is also a critical component of pulmonary artery remodeling associated with pulmonary hypertension (PH). However, the cellular and molecular mechanisms that drive vascular macrophage activation and their functional phenotype remain poorly defined. Using multiple levels of in vivo (bovine and rat models of hypoxia-induced PH, together with human tissue samples) and in vitro (primary mouse, rat, and bovine macrophages, human monocytes, and primary human and bovine fibroblasts) approaches, we observed that adventitial fibroblasts derived from hypertensive pulmonary arteries (bovine and human) regulate macrophage activation. These fibroblasts activate macrophages through paracrine IL-6 and STAT3, HIF1, and C/EBPβ signaling to drive expression of genes previously implicated in chronic inflammation, tissue remodeling, and PH. This distinct fibroblast-activated macrophage phenotype was independent of IL-4/IL-13-STAT6 and TLR-MyD88 signaling. We found that genetic STAT3 haplodeficiency in macrophages attenuated macrophage activation, complete STAT3 deficiency increased macrophage activation through compensatory upregulation of STAT1 signaling, and deficiency in C/EBPβ or HIF1 attenuated fibroblast-driven macrophage activation. These findings challenge the current paradigm of IL-4/IL-13-STAT6-mediated alternative macrophage activation as the sole driver of vascular remodeling in PH, and uncover a cross-talk between adventitial fibroblasts and macrophages in which paracrine IL-6-activated STAT3, HIF1α, and C/EBPβ signaling are critical for macrophage activation and polarization. Thus, targeting IL-6 signaling in macrophages by completely inhibiting C/EBPβ or HIF1α or by partially inhibiting STAT3 may hold therapeutic value for treatment of PH and other inflammatory conditions characterized by increased IL-6 and absent IL-4/IL-13 signaling. Copyright © 2014 by The American Association of Immunologists

Pulmonary arteriovenous malformation in cryptogenic liver

International Nuclear Information System (INIS)

Afzal, N.

2013-01-01

The cause in 10 - 20% cases of liver cirrhosis (LC) cannot be elucidated, and are thus termed cryptogenic. Pulmonary arteriovenous malformations (PAVMs) are relatively rare, but the most common anomaly involving the pulmonary tree. Although the rare correlation between LC and PAVM is well-known, there have been no reports of PAVMs occurring in cryptogenic LC. We report a case of PAVM that occurred in cryptogenic liver cirrhosis in a 3 years old male child. The child presented with complaints of malena, hematemesis and variceal bleed. The examination revealed a child with respiratory distress, irritability, tachycardia, clubbing and abdominal distention. He was worked up for recurrent variceal bleeding secondary to portal hypertension but the oxygen saturation during hospital stay kept deteriorating. The diagnosis of hepatopulmonary syndrome as the cause of persistent hypoxemia in the absence of other cardio-pulmonary causes was then made by enhanced echocardiogram using agitated saline. He improved significantly after liver transplantation performed abroad. At a 6 months follow-up, the child was stable with no evidence of intrapulmonary shunting on repeat echo. (author)

Pulmonary lymphangioleiomyomatosis as a pulmonary manifestation of tuberous sclerosis - a case report-

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Lee, Young Rahn; Kang, Eun Young; Lee, Nam Joon; Suh, Won Hyuck

1991-01-01

Pulmonary lymphangioleiomyomatosis is a very rare disease mainly arising in reproductive-aged women. Pulmonary lymphangioleiomyomatosis as a pulmonary involvement of tuberous sclerosis is found in only 1 out of 100 patients. Pulmonary involvement in pulmonary lymphangioleiomyomatosis itself and that as a pulmonary manifestation of tuberous sclerosis has been considered very similar with regard to clinical, radiologic, and pathologic manifestations. We report 1 case of pulmonary lymphangioleiomyomatosis as a pulmonary manifestation of tuberous sclerosis in a 39-year-old Korean woman

Impact of ECG gating in contrast-enhanced MR angiography for the assessment of the pulmonary veins and the left atrium anatomy

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Katoh, M.; Buecker, A.; Muehlenbruch, G.; Guenther, R.W.; Spuentrup, E.; Schauerte, P.

2006-01-01

Purpose: Implementation of ECG gating in contrast-enhanced MR angiography (ceMRA) for improved visualization of the pulmonary veins, the left atrium, and the thoracic vessels. Materials and Methods: CeMRA was performed on twelve patients with a history of recurrent atrial fibrillation for the purpose of an intra-individual comparison with and without ECG gating on a 1.5 Tesla MR system (Gyroscan Intera, Philips Medical Systems, Best, NL). Objective image quality parameters such as the signal-to-noise ratio (SNR) of the blood and the contrast-to-noise ratio (CNR) between the blood and myocardium or lung parenchyma were analyzed. The contour sharpness of the pulmonary veins, left atrium, ascending aorta, and pulmonary trunk was also measured. In addition, the artifact level was subjectively assessed by two observers blinded with respect to the sequence parameters. Statistically significant differences (p<0.05) between the procedures were analyzed using the Wilcoxon test and Pearson Chi-square test. Results: The use of ECG gating in ceMRA significantly reduced artifacts caused by cardiac motion and vessel pulsation. This in turn lead to a significant increase in the contour sharpness of the left atrium and the thoracic vessels. In addition, higher SNR and CNR were found using ECG-gated ceMRA compared to standard ceMRA. Conclusion: The use of ECG gating in ceMRA results in artifact-free and sharper delineation of the structures of the heart and thoracic vessels. (orig.)

Impact of ECG gating in contrast-enhanced MR angiography for the assessment of the pulmonary veins and the left atrium anatomy

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Katoh, M.; Buecker, A.; Muehlenbruch, G.; Guenther, R.W.; Spuentrup, E. [Klinik fuer Radiologische Diagnostik, Universitaetsklinikum RWTH Aachen (Germany); Schauerte, P. [Medizinische Klinik 1, Universitaetsklinikum RWTH Aachen (Germany)

2006-02-15

Purpose: Implementation of ECG gating in contrast-enhanced MR angiography (ceMRA) for improved visualization of the pulmonary veins, the left atrium, and the thoracic vessels. Materials and Methods: CeMRA was performed on twelve patients with a history of recurrent atrial fibrillation for the purpose of an intra-individual comparison with and without ECG gating on a 1.5 Tesla MR system (Gyroscan Intera, Philips Medical Systems, Best, NL). Objective image quality parameters such as the signal-to-noise ratio (SNR) of the blood and the contrast-to-noise ratio (CNR) between the blood and myocardium or lung parenchyma were analyzed. The contour sharpness of the pulmonary veins, left atrium, ascending aorta, and pulmonary trunk was also measured. In addition, the artifact level was subjectively assessed by two observers blinded with respect to the sequence parameters. Statistically significant differences (p<0.05) between the procedures were analyzed using the Wilcoxon test and Pearson Chi-square test. Results: The use of ECG gating in ceMRA significantly reduced artifacts caused by cardiac motion and vessel pulsation. This in turn lead to a significant increase in the contour sharpness of the left atrium and the thoracic vessels. In addition, higher SNR and CNR were found using ECG-gated ceMRA compared to standard ceMRA. Conclusion: The use of ECG gating in ceMRA results in artifact-free and sharper delineation of the structures of the heart and thoracic vessels. (orig.)

Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension

Directory of Open Access Journals (Sweden)

Caroline Claude

Full Text Available The ATP-binding cassette transporter MRP4 (encoded by ABCC4 regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells. MRP4/ABCC4 deficient mice display a reduction in smooth muscle cells proliferation and a prevention of pulmonary hypertension in response to hypoxia. We aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratracheal delivery of aerosolized adeno-associated virus 1 (AAV1.shMRP4 or AAV1.control in a monocrotaline-induced model of pulmonary hypertension in rats. Gene transfer was performed at the time of monocrotaline administration and the effect on the development of pulmonary vascular remodeling was assessed 35 days later. AAV1.shMRP4 dose-dependently reduced right ventricular systolic pressure and hypertrophy with a significant reduction with the higher doses (i.e., >1011 DRP/animal as compared to AAV1.control. The higher dose of AAV1.shMRP4 was also associated with a significant reduction in distal pulmonary arteries remodeling. AAV1.shMRP4 was finally associated with a reduction in the expression of ANF, a marker of cardiac hypertrophy. Collectively, these results support a therapeutic potential for downregulation of MRP4 for the treatment of pulmonary artery hypertension.

Preliminary studies of pulmonary perfusion scanning in patients with pulmonary hypertension

International Nuclear Information System (INIS)

Shi Rongfang; Liu Xiujie; Wang Yanqun

1986-01-01

A comparative analysis of pulmonary perfusion scanning through cardiac catheterization of 57 patients including 32 patients with congenital heart disease, 8 patients with chronic pulmonary thromboembolism and 7 patients with primary pulmonary hypertension is reported. The lung scintigram obtained with In-113m or Tc-99m-MAA represents the distribution of pulmonary blood. It has been found that the lung scintigram was abnormal in patients of congenital heart disease with pulmonary hypertension (i. e. pulmonary artery pressure between 41-80 mmHg) and the extent of radoiactive regional defects is proportional to the level of pulmonary hypertension. The results of the analysis indicated that pulmonary perfusion scanning being a noninvasive technique would be a useful method in evaluating the level of pulmonary hypertension in patients with left to right shunt before and after surgical operation

Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis

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Brady Kristen

2010-05-01

Full Text Available Abstract Background Previously we reported that mice deficient in toll-like receptor 4 (TLR-4 signalling were protected from diet-induced non-alcoholic steatohepatitis (NASH. Another member of the toll-like receptor family, TLR-2, has been shown to play a role in lipid trafficking via uptake of diacylated lipoproteins. However, a role for TLR-2 in NASH has not been elucidated. The objectives of the current study were to examine the influence of dietary fat quality and TLR-2 on NASH pathogenesis. Methods Steatohepatitis was induced in male Db, C57BL/6 and TLR-2-/- mice by feeding an L-amino acid-defined diet that was deficient in methionine and choline (MCDD. Mice fed the base diet supplemented with methionine and choline (control diet; CD were used as controls. To determine the role of fat quality, MCDD was enriched with polyunsaturated corn oil (PUFA or coconut oil that is comprised mostly of saturated fat (SAFA; the total amount of each fat was 112.9 g/kg of diet. After 8 weeks of feeding CD or MCDD, hepatic steatosis, inflammation and necrosis were evaluated in histological sections. Total RNA was extracted from frozen liver samples and mRNA expression of TNFα, collagen α1, IL-10, peroxisome proliferator-activated receptor-γ (PPAR-γ, TLR-4, and CD14, was analyzed via real-time PCR. Protein levels of TLR-2 were analyzed by western blot. Results Panlobular macrovessicular steatosis and diffuse leukocyte infiltration were noted in PUFA-fed Db mice. Histological scores demonstrated significantly less steatosis, inflammation and necrosis in SAFA-fed mice of all mouse strains. However, compared to wild type mice, hepatocellular damage was notably more severe in TLR-2-/- mice. Consistent with histological findings, mRNA expression of TNFα was elevated by approximately 3-fold in TLR-2-/- mice; PPAR-γ expression was blunted in this strain compared to wild type. Expression of the matrix protein collagen αI was also significantly higher in TLR-2

Airway reactivity in chronic obstructive pulmonary disease. Failure of in vivo methacholine responsiveness to correlate with cholinergic, adrenergic, or nonadrenergic responses in vitro.

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Taylor, S M; Paré, P D; Armour, C L; Hogg, J C; Schellenberg, R R

1985-07-01

This study aimed to determine whether in vivo airways hyperreactivity was manifested by either enhanced bronchial smooth muscle responses to contractile stimuli or by deficient responses to relaxant stimuli in vitro. Quantitative responses to nebulized methacholine were obtained in 12 human subjects prior to pulmonary resection. The provocative concentration of methacholine producing a 20% reduction in FEV1 (PC20) was calculated, and these values were compared with in vitro responses of bronchial smooth muscle strips from the surgical specimens. Both contractile cholinergic responses and relaxant nonadrenergic noncholinergic dose-response data were obtained for the in vitro bronchial specimens by electrical field stimulation. In addition, cumulative dose responses were obtained to exogenously added methacholine, the beta-adrenergic agonist salbutamol, and the adenylate cyclase activator forskolin. Despite a wide range of PC20 values, the in vivo airway responsiveness did not correlate with any of the in vitro responses examined, suggesting that airway reactivity is not due solely to the responsiveness of smooth muscle to contractile agonists nor to a localized deficiency in the nonadrenergic inhibitory system, beta-adrenergic inhibition, or abnormal cyclic-AMP-mediated pathways of relaxation.

Solitary pulmonary nodule by pulmonary hematoma under warfarin therapy

International Nuclear Information System (INIS)

Scheppach, W.; Kulke, H.; Liebau, G.; Braun, H.; Wuerzburg Univ.

1983-01-01

Pulmonary hematoma is a rare cause of a pulmonary nodule. Mostly it results from penetrating or blunt chest injuries. The case of a patient is reported, whose chest X-ray showed a pulmonary nodule suspected of malignancy. This patient was maintained permanently on anticoagulants (warfarin derivates) after cardiac valve replacement with a prosthesis. A definite diagnosis could not be established by non-invasive methods. A needle biopsy of the lung was impracticable because of the location of the pulmonary lesion; an exploratory thoracotomy could not be carried out due to a general indication of nonoperability. Control examinations showed that the pulmonary nodule had vanished completely within four months. In consideration of the patient's clinical situation it can be concluded that the pulmonary lesion was caused by a hematoma of the lung. (orig.) [de

Solitary pulmonary nodule by pulmonary hematoma under warfarin therapy

Energy Technology Data Exchange (ETDEWEB)

Scheppach, W.; Kulke, H.; Liebau, G.; Braun, H.

1983-06-01

Pulmonary hematoma is a rare cause of a pulmonary nodule. Mostly it results from penetrating or blunt chest injuries. The case of a patient is reported, whose chest X-ray showed a pulmonary nodule suspected of malignancy. This patient was maintained permanently on anticoagulants (warfarin derivates) after cardiac valve replacement with a prosthesis. A definite diagnosis could not be established by non-invasive methods. A needle biopsy of the lung was impracticable because of the location of the pulmonary lesion; an exploratory thoracotomy could not be carried out due to a general indication of nonoperability. Control examinations showed that the pulmonary nodule had vanished completely within four months. In consideration of the patient's clinical situation it can be concluded that the pulmonary lesion was caused by a hematoma of the lung.

Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

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Julia María Martínez Gómez

2016-03-01

Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

Introduction to Pulmonary Fibrosis

Science.gov (United States)

... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

History of pulmonary critical care nursing and where we are going.

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Lareau, Suzanne C; Mealer, Meredith

2012-09-01

Pulmonary critical care nurses have played a prominent role in the ICUs from the inception of critical care units. This article describes how the history of pulmonary critical care nursing has evolved and discusses a few of the challenges in the years to come: stress imposed by working in a critical care environment, enhancing the care of patients by altering patterns of sedation and promoting early mobilization, and dealing with increasing infection rates.

Expression of PDGF-beta receptor in broilers with pulmonary hypertension induced by cold temperature and its association with pulmonary vascular remodeling.

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Li, Jin-Chun; Pan, Jia-Qiang; Huang, Guo-Qing; Tan, Xun; Sun, Wei-Dong; Liu, Yan-Juan; Wang, Xiao-Long

2010-02-01

The purpose of the present study was to characterize the relationship between platelet-derived growth factor beta receptor (PDGF-beta receptor) expression and pulmonary vascular remodeling found in broilers subjected to cold temperature beginning at 14 days of age. One hundred and sixty-one-day-old mixed-sex Avian-2000 commercial broilers were randomly divided into a normal temperature group (control) and a cold temperature group (cold). All the birds were brooded in normal temperature up to day 14, with the lighting schedule at 24 h per day. Starting at day 14, birds in the cold group were moved to a pen in the cold house and subjected to low temperature, while birds in the control group were still brooded at normal temperature. On days 14, 23, 30, 37 and 44, the right/total ventricle weight ratio (RV/TV), packed cell volume (PCV), the vessel wall area to vessel total area ratio (WA/TA), mean media thickness in pulmonary arterioles (mMTPA) and the expression of PDGF-beta receptor in pulmonary arterioles were measured, respectively. Cumulative pulmonary hypertension syndrome (PHS) morbidity was recorded in each group. Cool ambient temperature increased PHS morbidity of broilers. The values of WA/TA and mMTPA were also increased significantly compared with control group. PCV values in the cold temperature group were elevated from days 30 to 44, and RV/TV ratios were increased on days 37 and 44. Cold exposure enhanced PDGF-beta receptor expression in pulmonary arterioles, and the PDGF-beta receptor expression was significantly correlated with pulmonary vascular remodeling that was dedicated by increased WA/TA and mMTPA. The results indicated that PDGF-beta and its receptor were involved in the underlying mechanisms of pulmonary vascular remodeling in pulmonary hypertensive broilers. Copyright 2009 Elsevier Ltd. All rights reserved.

Measurement of pulmonary vascular resistance of Fontan candidates with pulmonary arterial distortion by means of pulmonary perfusion imaging

International Nuclear Information System (INIS)

Park, In-Sam; Mizukami, Ayumi; Tomimatsu, Hirofumi; Kondou, Chisato; Nakanishi, Toshio; Nakazawa, Makoto; Momma, Kazuo

1998-01-01

We measured the distribution of blood flow to the right (R) and left lung (L) by means of pulmonary perfusion imaging and calculated pulmonary vascular resistance (Rp) in 13 patients, whose right and left pulmonary artery pressures were different by 2 to 9 mmHg due to pulmonary arterial distortion (5 interruption, 8 stenosis). The right lung/left lung blood flow ratio was determined and from the ratio and the total pulmonary blood flow, which was determined using the Fick's principle, the absolute values of right and left pulmonary blood flow were calculated. Using the right and left pulmonary blood flow and the right and left pulmonary arterial pressures, right and left pulmonary vascular resistance were calculated, separately. Vascular resistance of the whole lung (Rp) was then calculated using the following equation. 1/(Rp of total lung)=1/(Rp of right lung)+1/(Rp of left lung). Rp calculated from this equation was 1.8+/-0.8 U·m 2 and all values were less than 3 U·m 2 (range 0.3-2.8). Rp estimated from the conventional method using the total pulmonary blood flow and pulmonary arterial pressures, without using the right/left blood flow ratio, ranging from 0.4 to 3.8 U·m 2 and 5 of 13 patients showed Rp>3 U·m 2 . All patients underwent Fontan operation successfully. These data indicated that this method is useful to estimate Rp and to determine the indication of Fontan operation in patients with pulmonary arterial distortions. (author)

The Effects of Iodine Attenuation on Pulmonary Nodule Volumetry using Novel Dual-Layer Computed Tomography Reconstructions.

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den Harder, A M; Bangert, F; van Hamersvelt, R W; Leiner, T; Milles, Julien; Schilham, A M R; Willemink, M J; de Jong, P A

2017-12-01

To assess the effect of iodine attenuation on pulmonary nodule volumetry using virtual non-contrast (VNC) and mono-energetic reconstructions. A consecutive series of patients who underwent a contrast-enhanced chest CT scan were included. Images were acquired on a novel dual-layer spectral CT system. Conventional reconstructions as well as VNC and mono-energetic images at different keV levels were used for nodule volumetry. Twenty-four patients with a total of 63 nodules were included. Conventional reconstructions showed a median (interquartile range) volume and diameter of 174 (87 - 253) mm 3 and 6.9 (5.4 - 9.9) mm, respectively. VNC reconstructions resulted in a significant volume reduction of 5.5% (2.6 - 11.2%; p<0.001). Mono-energetic reconstructions showed a correlation between nodule attenuation and nodule volume (Spearman correlation 0.77, (0.49 - 0.94)). Lowering the keV resulted in increased volumes while higher keV levels resulted in decreased pulmonary nodule volumes compared to conventional CT. Novel dual-layer spectral CT offers the possibility to reconstruct VNC and mono-energetic images. Those reconstructions show that higher pulmonary nodule attenuation results in larger nodule volumes. This may explain the reported underestimation in nodule volume on non-contrast enhanced compared to contrast-enhanced acquisitions. • Pulmonary nodule volumes were measured on virtual non-contrast and mono-energetic reconstructions • Mono-energetic reconstructions showed that higher attenuation results in larger volumes • This may explain the reported nodule volume underestimation on non-contrast enhanced CT • Mostly metastatic pulmonary nodules were evaluated, results might differ for benign nodules.

Pulmonary Fibrosis Foundation

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... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

A case of intralobar pulmonary sequestration

International Nuclear Information System (INIS)

Hongo, Minoru; Kambayashi, TakayukiF; Okubo, Shinichi

1983-01-01

A 41 year-old male was admitted to our hospital, complaining of slight fever, dry cough and general fatigue. On auscultation, bubbling rales were audible at the mid to lower portion of left posterior chest. Plain chest roentgenogram showed multiple cystic shadows with an air-fluid level in the left lower lobe. An abnormal finger-like shadow, which extended from the left hemidiaphragm to the multiple cysts, was found on lateral chest tomogram. Bronchogram revealed cystic dilatation of left B6 and B10. Computed tomogram with contrast enhancement demonstrated multiple cysts and an abnormal round-shaped structure, consisted of high density material, in the left lower lung. At the level of 12 mm below the round-shaped structure, an abnormal finger-like structure contiguous to the thoracic descending aorta was demonstrated. The density of these abnormal structures was 80 Hounsfield units, which was the same as that of the descending aorta. Thoracic aortogram disclosed an abnormal artery arising from the thoracic descending aorta, just above the left hemidiaphragm, which proceeded to the left lower lung horizontally, and extended to superior direction and divided into multiple branches. These vessels drained into the left atrium via left lower pulmonary vein. Diagnosis of intralobar pulmonary sequestration was confirmed by operation and consequently, the sequestered lung and the abnormal artery were successfully removed. It is emphasized that computed tomography with contrast enhancement is useful to detect the abnormal artery of pulmonary sequestration and that this method should be used to evaluate the vascular relationship of lung lesions. (author)

Basics concepts and clinical applications of oxygen-enhanced MR imaging

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Hatabu, Hiroto

2007-01-01

Oxygen-enhanced MR imaging is a new technique, and its physiological significance has not yet been fully elucidated. This review article covers (1) the theory of oxygen enhancement and its relationship with respiratory physiology; (2) design for oxygen-enhanced MR imaging sequencing; (3) a basic study of oxygen-enhanced MR imaging in animal models and humans; (4) a clinical study of oxygen-enhanced MR imaging; and (5) a comparison of advantages and disadvantages of this technique with those of hyperpolarized noble gas MR ventilation imaging. Oxygen-enhanced MR imaging provides not only the ventilation-related, but also respiration-related information. Oxygen-enhanced MR imaging has the potential to replace nuclear medicine studies for the identification of regional pulmonary function, and many investigators are now attempting to adapt this technique for routine clinical studies. We believe that further basic studies as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR imaging for the future of pulmonary functional imaging and its usefulness for diagnostic radiology and pulmonary medicine

Pulmonary agenesis

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Oyola, Mercedes; Pontificia Universidad Javeriana; Gordillo, Gisel; Pontificia Universidad Javeriana; García, Carlos A.; Pontificia Universidad Javeriana; Torres, David; Pontificia Universidad Javeriana

2009-01-01

Pulmonary agenesis is an infrequent pathology which occurs predominantly among females with no lateral preference. We report on the case of a newborn male diagnosed with prenatal diaphragm hernia though at birth seemed more likely either to be a congenital cystic adenomatoid malformation (congenital pulmonary airway malformation) or pulmonary agenesis. The patient died six days after birth and necropsy confirmed pulmonary agenesis. La agenesia pulmonar es una alteración poco frecuente, con...

Pulmonary Artery Dissection: A Fatal Complication of Pulmonary Hypertension

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Chuanchen Zhang

2016-01-01

Full Text Available Pulmonary artery dissection is extremely rare but it is a really life-threatening condition when it happens. Most patients die suddenly from major bleeding or tamponade caused by direct rupture into mediastinum or retrograde into the pericardial sac. What we are reporting is a rare case of a 46-year-old female patient whose pulmonary artery dissection involves both the pulmonary valve and right pulmonary artery. The patient had acute chest pain and severe dyspnea, and the diagnosis of pulmonary artery dissection was confirmed by ultrasonography and CT angiography. Moreover, its etiology, clinical manifestations, and management are also discussed in this article.

Successful Obstetric Outcome in Dextrocardia with Situs Inversus and Moderate Pulmonary Hypertension- Rare Case

OpenAIRE

Deepika,; Wadhwa, Leena; Shekhar, Chandna; Saini, Jyoti; Chetani, Monica

2016-01-01

Situs inversus is a rare congenital anomaly, which is characterized by right sided heart (Dextrocardia) and inversely rotated visceral organs of abdomen. In present case, the patient reported with G3p2l2, 34 weeks of gestational period along with breathlessness accompanied and labour pains. On further investigation, she was diagnosed as dextrocardia with situs inversus and moderate pulmonary artery hypertension along with severe iron deficiency anaemia. Patient had normal vaginal delivery wit...

Retrograde pulmonary arteriography

International Nuclear Information System (INIS)

Calcaterra, G.; Lam, J.; Losekoot, T.G.

1984-01-01

The authors performed retrograde pulmonary arteriography by means of a pulmonary venous wedge injection in 10 patients with no demonstrable intrapericardial pulmonary arteries by 'conventional' angiographic techniques. In all cases but one, the procedure demonstrated the feasibility of a further operation. No complications were observed. Retrograde pulmonary arteriography is an important additional method for determining the existence of surgically accessible pulmonary arteries when other techniques have failed. (Auth.)

Mitochondrial Complex IV Subunit 4 Isoform 2 Is Essential for Acute Pulmonary Oxygen Sensing.

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Sommer, Natascha; Hüttemann, Maik; Pak, Oleg; Scheibe, Susan; Knoepp, Fenja; Sinkler, Christopher; Malczyk, Monika; Gierhardt, Mareike; Esfandiary, Azadeh; Kraut, Simone; Jonas, Felix; Veith, Christine; Aras, Siddhesh; Sydykov, Akylbek; Alebrahimdehkordi, Nasim; Giehl, Klaudia; Hecker, Matthias; Brandes, Ralf P; Seeger, Werner; Grimminger, Friedrich; Ghofrani, Hossein A; Schermuly, Ralph T; Grossman, Lawrence I; Weissmann, Norbert

2017-08-04

Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as a critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and the mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing, remain unresolved. To investigate the role of the pulmonary-specific isoform 2 of subunit 4 of the mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling. Isolated ventilated and perfused lungs from Cox4i2 -/- mice lacked acute HPV. In parallel, pulmonary arterial smooth muscle cells (PASMCs) from Cox4i2 -/- mice showed no hypoxia-induced increase of intracellular calcium. Hypoxia-induced superoxide release which was detected by electron spin resonance spectroscopy in wild-type PASMCs was absent in Cox4i2 -/- PASMCs and was dependent on cysteine residues of Cox4i2. HPV could be inhibited by mitochondrial superoxide inhibitors proving the functional relevance of superoxide release for HPV. Mitochondrial hyperpolarization, which can promote mitochondrial superoxide release, was detected during acute hypoxia in wild-type but not Cox4i2 -/- PASMCs. Downstream signaling determined by patch-clamp measurements showed decreased hypoxia-induced cellular membrane depolarization in Cox4i2 -/- PASMCs compared with wild-type PASMCs, which could be normalized by the application of hydrogen peroxide. In contrast, chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling were not or only slightly affected by Cox4i2 deficiency, respectively. Cox4i2 is essential for acute but not chronic pulmonary oxygen sensing by triggering mitochondrial hyperpolarization and release of mitochondrial superoxide which, after conversion

Ablation of the Leptin receptor in Myeloid Cells Impairs Pulmonary Clearance of Streptococcus Pneumoniae and Alveolar Macrophage Bactericidal Function.

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Mancuso, Peter; Curtis, Jeffrey L; Freeman, Christine M; Peters-Golden, Marc; Weinberg, Jason B; Myers, Martin G

2018-03-22

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiologic functions including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with S. pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post-infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AM)s from LysM-LepRb-KO mice in vitro, and was associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results, confirm our previous observations in leptin-deficient (ob/ob) and fasted mice, and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, are responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.

Assessment of anatomic relation between pulmonary perfusion and morphology in pulmonary emphysema with breath-hold SPECT-CT fusion images

International Nuclear Information System (INIS)

Suga, Kazuyoshi; Kawakami, Yasuhiko; Iwanaga, Hideyuki; Hayashi, Noriko; Seto, Akiko; Matsunaga, Naofumi

2008-01-01

Anatomic relation between pulmonary perfusion and morphology in pulmonary emphysema was assessed on deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images. Subjects were 38 patients with pulmonary emphysema and 11 non-smoker controls, who successfully underwent DIBrH and non-BrH perfusion SPECT using a dual-headed SPECT system during the period between January 2004 and June 2006. DIBrH SPECT was three-dimensionally co-registered with DIBrH CT to comprehend the relationship between lung perfusion defects and CT low attenuation areas (LAA). By comparing the appearance of lung perfusion on DIBrH with non-BrH SPECT, the correlation with the rate constant for the alveolar-capillary transfer of carbon monoxide (DLCO/VA) was compared between perfusion abnormalities on these SPECTs and LAA on CT. DIBrH SPECT provided fairly uniform perfusion in controls, but significantly enhanced perfusion heterogeneity when compared with non-BrH SPECT in pulmonary emphysema patients (P<0.001). The reliable DIBrH SPECT-CT fusion images confirmed more extended perfusion defects than LAA on CT in majority (73%) of patients. Perfusion abnormalities on DIBrH SPECT were more closely correlated with DLCO/VA than LAA on CT (P<0.05). DIBrH SPECT identifies affected lungs with perfusion abnormality better than does non-BrH SPECT in pulmonary emphysema. DIBrH SPECT-CT fusion images are useful for more accurately localizing affected lungs than morphologic CT alone in this disease. (author)

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli.

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Gomez, Fernando; Monsalve, Gabriela C; Tse, Vincent; Saiki, Ryoichi; Weng, Emily; Lee, Laura; Srinivasan, Chandra; Frand, Alison R; Clarke, Catherine F

2012-12-20

Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli

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Gomez Fernando

2012-12-01

Full Text Available Abstract Background Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. Results The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. Conclusions The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor

Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro: Pi*ZQ0gaia – Q0gaia allele

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M.J. Oliveira

2015-11-01

Full Text Available Severe alpha-1 antitrypsin deficiency (AATD is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0 alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C, which was named Q0gaia (Pi*ZQ0gaia. Q0gaia is associated with very low or no detectable serum concentrations of AAT. Keywords: Alpha-1 antitrypsin deficiency, Null allele, COPD

IMMUNOTHERAPY IN TREATMENT OF PULMONARY TUBERCULOSIS IN ADOLESCENTS

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I. I. Lvova

2014-01-01

Full Text Available Comprehensive examination of 62 adolescents, hospitalized for pulmonary tuberculosis, established high spread of clinical and laboratory markers of secondary immune deficiency: chronic diseases of ear, throat and nose (59,6%, recurrent infection caused by the herpes simplex viruses (SPGV (55,8% ; serological SPGV activation (90,4% and cytomegalovirus infection (CMV (94,2%; absolute lymphopenia (53,8%, low level and lack of interferon-alpha (28,9% and interferongamma (76,9%. Validity, effectiveness and safety of modern technology immunization with interferon -α-2b (VIFERON® 3 million IU and 1 million IU suppositories in 1 month course in the complex treatment of pulmonary tuberculosis was proved with a random research by a «case-control» method. Significant positive clinical and laboratory dynamics was registered: increase in body weight in 84,6 % of adolescents; reduction in the frequency of arrhythmias; increase absolute lymphocyte count (46,1%, decrease in serological SPGV activation (30,8% and CMV infection (61,5% increase in the amount of interferon-alpha (61,5%, and interferon-gamma (61,5% and absence of intolerance and 3 times less undesirable effects of chemotherapy.

Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

International Nuclear Information System (INIS)

Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

2015-01-01

Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding

Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

Energy Technology Data Exchange (ETDEWEB)

Yasuda-Yamahara, Mako [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Kume, Shinji, E-mail: skume@belle.shiga-med.ac.jp [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Koya, Daisuke [Department of Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan); Haneda, Masakzu [Division of Metabolism and Biosystemic Science, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)

2015-09-18

Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension.

Science.gov (United States)

Castelain, V; Hervé, P; Lecarpentier, Y; Duroux, P; Simonneau, G; Chemla, D

2001-03-15

The purpose of this time-domain study was to compare pulmonary artery (PA) pulse pressure and wave reflection in chronic pulmonary thromboembolism (CPTE) and primary pulmonary hypertension (PPH). Pulmonary artery pressure waveform analysis provides a simple and accurate estimation of right ventricular afterload in the time-domain. Chronic pulmonary thromboembolism and PPH are both responsible for severe pulmonary hypertension. Chronic pulmonary thromboembolism and PPH predominantly involve proximal and distal arteries, respectively, and may lead to differences in PA pressure waveform. High-fidelity PA pressure was recorded in 14 patients (7 men/7 women, 46 +/- 14 years) with CPTE (n = 7) and PPH (n = 7). We measured thermodilution cardiac output, mean PA pressure (MPAP), PA pulse pressure (PAPP = systolic - diastolic PAP) and normalized PAPP (nPAPP = PPAP/MPAP). Wave reflection was quantified by measuring Ti, that is, the time between pressure upstroke and the systolic inflection point (Pi), deltaP, that is, the systolic PAP minus Pi difference, and the augmentation index (deltaP/PPAP). At baseline, CPTE and PPH had similar cardiac index (2.4 +/- 0.4 vs. 2.5 +/- 0.5 l/min/m2), mean PAP (59 +/- 9 vs. 59 +/- 10 mm Hg), PPAP (57 +/- 13 vs. 53 +/- 13 mm Hg) and nPPAP (0.97 +/- 0.16 vs. 0.89 +/- 0.13). Chronic pulmonary thromboembolism had shorter Ti (90 +/- 17 vs. 126 +/- 16 ms, p PPAP (0.26 +/- 0.01 vs. 0.09 +/- 0.07, p < 0.01). Our study indicated that: 1) CPTE and PPH with severe pulmonary hypertension had similar PA pulse pressure, and 2) wave reflection is elevated in both groups, and CPTE had increased and anticipated wave reflection as compared with PPH, thus suggesting differences in the pulsatile component of right ventricular afterload.

Hemodynamic Change in Pulmonary Vein Stenosis after Radiofrequency Ablation: Assessment with Magnetic Resonance Angiography

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Yun, Doyoung; Jung, Jung Im; Oh, Yong Seog; Youn, Ho Joong [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2012-11-15

We present a case of pulmonary vein (PV) stenosis after radio-frequency (RF) ablation, in which a hemodynamic change in the pulmonary artery was similar to that of congenital PV atresia on time-resolved contrast-enhanced magnetic resonance angiography (TR-MRA). A 48-year-old man underwent RF ablation due to atrial fibrillation. The patient subsequently complained of hemoptysis, dyspnea on exertion, and right chest pain. Right PV stenosis after catheter ablation was diagnosed through chest computed tomography and lung perfusion scan. Pulmonary TR-MRA revealed the pulmonary artery via systemic arterial collaterals and draining systemic collateral veins. On a velocity-encoded cine image, the flow direction of the right pulmonary artery was reversed in the diastolic phase and the left pulmonary artery demonstrated continuous forward flow throughout the cardiac cycle. These hemodynamic changes were similar to those seen in congenital unilateral PV atresia.

The effect of pulmonary rehabilitation program on quality of life of elderly patients with chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Neda Mirbagher-Ajorpaz

2011-03-01

Full Text Available Background: Considering the prevalence of chronic obstructive pulmonary disease (COPD and its well-known complications; different studies indicate the success of rehabilitation techniques to improve quality of life for those patients. The present study was conducted to determine the effect of the implementation of pulmonary rehabilitation techniques on quality of life in patients with COPD.Materials and Method: This quasi-experimental research was performed in the selected teaching hospitals in Isfahan on 80 elderly patients with COPD with moderate intensity during their 85-86 years. The patients divided randomly into two groups (40 patients in case group and 40 patients in control group. The disease severity was evaluated based on spirometry results. Data were collected by using quality of life questionnaire (SF-12. First, the quality of life of patients in both groups was evaluated by SF-12 and then the 20 minutes pulmonary rehabilitation programs in the case group were performed every morning and evening for two months. At the end of two months, the qualities of life in both groups were measured again. The results were analyzed using SPSS-10 software. Results: The results showed that there is a significant direct relationship between some demographic characteristics and their quality of life score (p=0.03. Pulmonary rehabilitation program enhanced the quality of life in those patients (p=0.01. Conclusion: Regarding these findings, it should be consider that demographic characteristics of patients and their rehabilitation programs should be included the pulmonary rehabilitation program to improve quality of life

[Treatment of bronchial obstruction in patients with pulmonary tuberculosis].

Science.gov (United States)

Shmelev, E I; Kuklina, G M; Kalinina, E E

2004-01-01

Whether the main points of treatment for bronchial obstructive syndrome (BOS) in chronic obstructive lung disease (COLD) can be adapted for patients with pulmonary tuberculosis (PT) was studied. For this purpose, 435 patients with PT with signs of BOS (forced expiratory volume at 1 second (FEV1) 70% of the normal values; 2) 229 patients with FEV1 69-50%; 3) 102 patients with FEV1 bronchial obstructive syndrome in patients with pulmonary tuberculosis was highly effective, promotes the amelioration of the degree of respiratory symptoms in patients with IPT by 2 to 8 times, in those with FCPT by more than 2-3 times, and in those with PS by 1.45-10 times. The differences in the efficiency of bronchodilator therapy depend on the baseline level of bronchial obstruction. In patients with pulmonary tuberculosis concurrent with BO, the use of current inhalation bronchodilator therapy results in a substantial increase in FEV1, which differentiates BOS in PT from COLD. The use of the proposed therapy in the multimodality treatment of patients with pulmonary tuberculosis showed no statistically significant differences in the changes in the degree of X-ray symptoms while this therapy permits acceleration of abacillation in patients with IPT by 16.8% and in those with FCPT by 14.8%. Effective bronchodilator therapy considerably enhances life quality in patients. Thus, early systematic and long-term performance of the bronchodilator therapy, based on the principles of bronchodilator therapy for COLD, in patients with PT concurrent with BOS may substantially enhance the efficiency of treatment in this category of patients.

Survival curves of irradiated glutathione-deficient human fibroblasts: indication of a reduced enhancement of radiosensitivity by oxygen and misonidazole

International Nuclear Information System (INIS)

Midander, J.; Deschavanne, P.J.; Malaise, E.P.; Revesz, L.

1982-01-01

Fibroblasts derived from a patient with 5-oxoprolinuria are genetically deficient in glutathione synthetase. This deficiency causes a dramatic decrease in intracellular glutathione (GSH) level. The radiosensitivity of GSH deficient cells (GSH) was studied in vitro using colony forming ability as an endpoint. Cells with normal GSH level, obtained from the healthy brother of the patient, were used as controls. When irradiated in 95% air-5% CO 2 , GSH - cells are slightly but significantly more radiosensitive than GSH + controls (dose modifying factor (DMF) of 1.2). When irradiated in argon, the survival curve of GSH - cells indicates an oxygen enhancement ratio (OER) of 1.5 when compared to the curve obtained in oxic conditions. The OER of control cells in the same conditions is 2.9. In comparison to results obtained in air, 100% oxygen moderately increases the radiosensitivity of GSH + cells (DMF 1,23), while it has a very low effect on GSH - cells (DMF 1.06). These results suggest that intracellular GSH plays an essential protective role in hypoxia, its effect is reduced in air and practically disappears in 100% oxygen. When cells are incubated with 8 mM misonidazole 2 hours before irradiation, the drug has a much greater sensitizing effect on GSH + cells (DMF 2.33) than on GSH - cells (DMF 1.55). The results demonstrate that intracellular GSH level plays a major role in the response of hypoxic cells, irradiated either alone or in the presence of misonidazole

Storage Pool Deficiencies

Science.gov (United States)

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

[Pulmonary function in patients with infiltrative pulmonary tuberculosis].

Science.gov (United States)

Nefedov, V B; Popova, L A; Shergina, E A

2007-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), R(aw), R(in),, R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 103 patients with infiltrative pulmonary tuberculosis. Pulmonary dysfunction was detected in 83.5% of the patients. Changes were found in lung volumes and capacities in 63.1%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 60.2 and 41.7%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC and FVC, and decreased and increased TGV and TLC; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, FEV1/VC% and increased R(aw) R(in), and R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, and PaO2 and decreased and increased PaCO2. The magnitude of the observed functional changes was generally slight. Significant disorders were observed rarely and very pronounced ones were exceptional.

[Pulmonary function in patients with disseminated pulmonary tuberculosis].

Science.gov (United States)

Nefedov, V B; Shergina, E A; Popova, L A

2007-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25%, MEF50%, MEF75%, TLS, TGV, pulmonary residual volume (PRV), Raw, Rin, Rex, DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 29 patients with disseminated pulmonary tuberculosis. Pulmonary dysfunction was detected in 93.1% of the patients. Changes were found in lung volumes and capacities in 65.5%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 79.3 and 37.9%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC, FVC, and TLS, decreased and increased TGV; impaired bronchial patency presented as decreased PEF, MEF25%, MEF50%, MEF75%, and FEV1/VC% and increased Raw, Rin, and Rex; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SS and PaO2 and decreased and increased PaCO2. The observed functional changes varied from slight to significant and pronounced with a preponderance of small disorders, a lower detection rate of significant disorders, and rare detection of very pronounced ones.

Simvastatin enhances bone morphogenetic protein receptor type II expression

International Nuclear Information System (INIS)

Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N.

2006-01-01

Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function

Pulmonary sequestration: diagnosis with three dimensional reconstruction using spiral CT

International Nuclear Information System (INIS)

Nie Yongkang; Zhao Shaohong; Cai Zulong; Yang Li; Zhao Hong; Zhang Ailian; Huang Hui

2003-01-01

Objective: To evaluate the role of three dimensional (3D) reconstruction using spiral CT in the diagnosis of pulmonary sequestration. Methods: Ten patients with pulmonary sequestration were analyzed. The diagnoses were confirmed by angiography in 2 patients, by operation in 2 patients, and by CT angiography in 6 patients. All patients were examined with Philips SR 7000 or GE Lightspeed Plus scanner. CT images were transferred to a workstation and 3D reconstruction was performed. All images were reviewed and analyzed by two radiologists. Results: Among 10 patients, the pulmonary sequestration was in the right lower lobe in 1 patient and in the left lower lobe in 9 patients. Anomalous systemic arteries originated from thoracic aorta in 8 patients and from celiac artery in 2 patients. On plain CT scan, there were 4 patients with patchy opacities, 3 patients with hilar mass accompanying vascular engorgement and profusion in adjacent parenchyma, 2 patients with finger-like appendage surrounded by hyper-inflated lung, and 1 patient with lung mass-like lesion. Enhanced CT revealed anomalous systemic arteries in 9 patients and drainage vein in 7 patients. Maximum intensity projection (MIP) and curvilinear reconstruction could depict the abnormal systemic artery and drainage vein in sequestration. Surface shadow display (SSD) and volume rendering (VR) could delineate the anomalous systemic artery. Conclusion: 3D reconstruction with enhanced spiral CT can depict anomalous systemic artery and drainage vein and it is the first method of choice in diagnosing pulmonary sequestration

Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease is Enhanced by Nrf2 Agonists.

NARCIS (Netherlands)

Bewley, Martin A; Budd, Richard C; Ryan, Eilise; Cole, Joby; Collini, Paul; Marshall, Jennifer; Kolsum, Umme; Beech, Gussie; Emes, Richard D; Tcherniaeva, Irina; Berbers, Guy A M; Walmsley, Sarah R; Donaldson, Gavin; Wedzicha, Jadwiga A; Kilty, Iain; Rumsey, William; Sanchez, Yolanda; Brightling, Christopher E; Donnelly, Louise E; Barnes, Peter J; Singh, Dave; Whyte, Moira K B; Dockrell, David H

2018-01-01

Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined.

CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

International Nuclear Information System (INIS)

Taslakian, Bedros; Latson, Larry A.; Truong, Mylene T.; Aaltonen, Eric; Shiau, Maria C.; Girvin, Francis; Alpert, Jeffrey B.; Wickstrom, Maj; Ko, Jane P.

2016-01-01

Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

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Taslakian, Bedros, E-mail: bedros.taslakian@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Latson, Larry A., E-mail: larry.latson@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Truong, Mylene T., E-mail: mtruong@mdanderson.org [Department of Radiology, University of Texas, MD Anderson Cancer Center, TX (United States); Aaltonen, Eric, E-mail: Eric.Aaltonen@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Shiau, Maria C., E-mail: Maria.Shiau@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Girvin, Francis, E-mail: Francis.Girvin@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Alpert, Jeffrey B., E-mail: Jeffrey.Alpert@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Wickstrom, Maj, E-mail: Maj.Wickstrom@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Ko, Jane P., E-mail: Jane.Ko@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States)

2016-11-15

Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

Melatonin enhances cold tolerance in drought-primed wild-type and abscisic acid-deficient mutant barley.

Science.gov (United States)

Li, Xiangnan; Tan, Dun-Xian; Jiang, Dong; Liu, Fulai

2016-10-01

Melatonin is involved in multiple plant developmental processes and various stress responses. To explore the roles of melatonin played as well as its association with abscisic acid (ABA) in a process of drought priming-induced cold tolerance (DPICT), a wild-type barley and its ABA-deficient mutant Az34 counterpart were selected for comparison, in which the effects of melatonin application (either foliarly or rhizospherically) and/or drought priming on the cold tolerance of both types of barleys were systematically investigated. It was demonstrated that the early drought priming induced an increase of endogenous melatonin production, which is not ABA dependent. In addition, exogenously applied melatonin resulted in higher ABA concentration in the drought-primed plants than in the nonprimed plants when exposed to cold stress, indicating that ABA responded in a drought-dependent manner. The interplay of melatonin and ABA leads to plants maintaining better water status. Drought priming-induced melatonin accumulation enhanced the antioxidant capacity in both chloroplasts and mitochondria, which sustained the photosynthetic electron transport in photosynthetic apparatus of the plants under cold stress. These results suggest that the exogenous melatonin application enhances the DPICT by modulating subcellular antioxidant systems and ABA levels in barley. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lack of oxygen effect in glutathione-deficient human cells in culture

International Nuclear Information System (INIS)

Edgren, M.; Larsson, A.; Nilsson, K.; Revesz, L.; Scott, O.C.A.

1980-01-01

The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks. (author)

The diagnosis and treatment of two kinds of pulmonary embolism complications after interventional therapy

International Nuclear Information System (INIS)

Su Hongying; Xiao Liang; Zhong Hongshan; Xu Ke; Zheng Yanbo; Lu Zaiming

2008-01-01

Objective: To summarize the different types, clinical manifestation, treatment and prognosis of pulmonary embolism after interventional therapy in order to promote the diagnosis and treatment for the severe complication. Methods: The cases of pulmonary embolism complications after interventional therapy were collected from three hospitals between 1998 and 2005. The patients were divided into two types of iodized oil and thrombus pulmonary embolism according to the different types of the embolus. The experience of the clinical manifestation, diagnosis and treatment were summarized. Results: Ten patients with pulmonary embolism complication after interventional therapy were collected, including five with thrombus pulmonary embolism and four with iodized oil pulmonary embolism. All 5 cases of the thrombus pulmonary embolism suffered burst dyspnea and apsychia, two died and the others recovered or turned better. Aggravating dyspnea without shock occurred in the five iodized oil pulmonary embolism cases, 1 to 3 days after interventional therapy. The symptoms disappeared 15 to 50 days after combined therapy including majorly oxygen supply therapy. Conclusion: Pulmonary embolism is an emergent and severe complication after interventional therapy including acute thrombus pulmonary embolism without deep vein thrombosis which can be effectively treated be effectively treated with maintaining effective circulation and thrombolysis; and iodized oil pulmonary embolism with slow onsets could disappear within 1 month after combined therapy with mainly oxygen supplying therapy. The diagnosis and antidiastole mainly rely on enhancement of CT scan. (authors)

Dynamic CT findings of pulmonary hamartoma: A comparison with histopathologic findings

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Cho, Wanglae; Jeong, Yeon Joo; Lee, Chang Hun; Lee, Ji Won; Kim, Yeong Dae [Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan (Korea, Republic of); Kim, Kun Il [Dept. of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine and Medical Research Institute, Yangsan (Korea, Republic of)

2013-12-15

Describe the dynamic CT findings of pulmonary hamartoma and to compare these findings with histopathologic findings. he Institutional Review Board approved this retrospective study and the requirement for patient informed consent was waived. The hemodynamic CT features of 11 patients (M : F = 6 : 5; mean age, 53.6 years) with pathologically proven pulmonary hamartoma were evaluated. All 11 patients underwent enhanced dynamic CT using a helical technique. A series of images were obtained throughout each nodule with 2.5-mm collimation at 0, 30, 60, 90 and 120 seconds and at 4, 5 and 15 minutes after an intravenous injection of contrast medium. Extents and patterns of enhancement were correlated with histologic tumor components. ll 11 tumors showed persistent enhancement with variable degrees of net enhancement [mean tumor peak enhancement, 48.6 ± 19.0 Hounsfield unit (HU); mean tumor net enhancement, 31.9 ± 11.8 HU] and thick capsular and septal enhancement. Histologically, all 11 tumors were composed of mature cartilage and loose mesenchymal tissue. A significant positive correlation was found between the net enhancement values and loose connective tissue component percentages (r = 0.749, p = 0.008); further, a negative correlation was found between the net enhancement values and cartilaginous component percentages (r = -0.813, p = 0.002). n dynamic CT, hamartoma exhibited persistent enhancement without washout as well as thick capsular and septal enhancements. Net enhancement values were found to be positively correlated with the proportion of the loose connective tissue component. Thick capsular and septal enhancements were attributed histopathologically to loose connective tissue, separating tumors into cartilaginous lobules.

Dynamic CT findings of pulmonary hamartoma: A comparison with histopathologic findings

International Nuclear Information System (INIS)

Cho, Wanglae; Jeong, Yeon Joo; Lee, Chang Hun; Lee, Ji Won; Kim, Yeong Dae; Kim, Kun Il

2013-01-01

Describe the dynamic CT findings of pulmonary hamartoma and to compare these findings with histopathologic findings. he Institutional Review Board approved this retrospective study and the requirement for patient informed consent was waived. The hemodynamic CT features of 11 patients (M : F = 6 : 5; mean age, 53.6 years) with pathologically proven pulmonary hamartoma were evaluated. All 11 patients underwent enhanced dynamic CT using a helical technique. A series of images were obtained throughout each nodule with 2.5-mm collimation at 0, 30, 60, 90 and 120 seconds and at 4, 5 and 15 minutes after an intravenous injection of contrast medium. Extents and patterns of enhancement were correlated with histologic tumor components. ll 11 tumors showed persistent enhancement with variable degrees of net enhancement [mean tumor peak enhancement, 48.6 ± 19.0 Hounsfield unit (HU); mean tumor net enhancement, 31.9 ± 11.8 HU] and thick capsular and septal enhancement. Histologically, all 11 tumors were composed of mature cartilage and loose mesenchymal tissue. A significant positive correlation was found between the net enhancement values and loose connective tissue component percentages (r = 0.749, p = 0.008); further, a negative correlation was found between the net enhancement values and cartilaginous component percentages (r = -0.813, p = 0.002). n dynamic CT, hamartoma exhibited persistent enhancement without washout as well as thick capsular and septal enhancements. Net enhancement values were found to be positively correlated with the proportion of the loose connective tissue component. Thick capsular and septal enhancements were attributed histopathologically to loose connective tissue, separating tumors into cartilaginous lobules.

CT and PET-CT of a Dog with Multiple Pulmonary Adenocarcinoma

Science.gov (United States)

KIM, Jisun; KWON, Seong Young; CENA, Rohani; PARK, Seungjo; OH, Juyeon; OUI, Heejin; CHO, Kyoung-Oh; MIN, Jung-Joon; CHOI, Jihye

2013-01-01

ABSTRACT A 10-year-old, intact female Yorkshire terrier had multiple pulmonary nodules on thoracic radiography and ultrasonography with no lesions elsewhere. Computed tomography (CT) and positron emission tomography and computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) were performed to identify metastasis and undetected primary tumors. On CT examination, pulmonary nodules had a hypoattenuating center with thin peripheral enhancement, suggesting ischemic or necrotizing lesion. In PET-CT at 47 min after intravenous injection of 11.1 MBq/kg of FDG, the maximum standardized uptake value of each pulmonary nodule was about from 3.8 to 6.4. There were no abnormal lesions except for four pulmonary nodules on the CT and PET-CT. Primary lung tumor was tentatively diagnosed, and palliative therapy using 2 mg/kg tramadol and 2.2 mg/kg carprofen twice per day was applied. After the dog’s euthanasia due to deteriorated clinical signs and poor prognosis, undifferentiated pulmonary adenocarcinoma was diagnosed through histopathologic and immunochemistry examination. To the best of the authors’ knowledge, this is the first study of CT and PET-CT features of canine pulmonary adenocarcinoma. In this case, multiple pulmonary adenocarcinoma could be determined on the basis of FDG PET-CT through screening the obvious distant metastasis and/or lymph node invasions and excluding unknown primary tumors. PMID:24389742

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

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Jung Hyun Park

2017-01-01

Full Text Available Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2 regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA- transfected Lewis lung carcinoma (LLC cells and idh2-deficient (idh2−/− mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration.

Science.gov (United States)

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP + -dependent isocitrate dehydrogenase ( idh2 ) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2 -deficient ( idh2 -/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2 -/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Estimation of pulmonary water distribution and pulmonary congestion by computed tomography

International Nuclear Information System (INIS)

Morooka, Nobuhiro; Watanabe, Shigeru; Masuda, Yoshiaki; Inagaki, Yoshiaki

1982-01-01

Computed tomography (CT) of the lung in normal subjects and patients with congestive heart failure was performed in the supine position with deep inspiration to obtain pulmonary CT values and images. The mean CT value in normal subjects was higher in the posterior than anterior lung field, presumably because blood vessels were more dilated in the former than the latter due to the effects of gravity. The mean pulmonary CT value in patients with congestive heart failure was significantly increased possibly due to an increase in blood flow per unit lung volume arising from either pulmonary congestion or pulmonary interstitial and alveolar edema. The mean pulmonary CT value increased parallel to the severity of pulmonary congestion, interstitial or alveolar edema and was well correlated with the pulmonary arterial wedge pressure, indicating that such a correlation was a valuable tool in assessing therapeutic effects. The results of the present study indicatethat pulmonary CT is useful for the noninvasive estimation of intrapulmonary water content and its distribution, thereby providing an effective diagnostic clue to various conditions in congestive heart failure. (author)

Is zinc deficiency a risk factor for atherosclerosis?

Science.gov (United States)

Beattie, John H; Kwun, In-Sook

2004-02-01

The development of atherosclerosis is influenced by genetic, lifestyle and nutritional risk factors. Zn and metallothionein deficiency can enhance oxidative-stress-related signalling processes in endothelial cells, and since changes in available plasma Zn may affect the Zn status of the endothelium, Zn deficiency could be a risk factor for IHD. Although the association of Zn with many proteins is essential for their function, three key signalling processes are highlighted as being principal targets for the effect of Zn deficiency: the activation of NF-kappaB, the activation of caspase enzymes and the signalling of NO. The need to develop a reliable indicator of Zn status is critical to any epidemiological approach for studying the relationship between Zn status and disease incidence. Studies using appropriate animal models and investigating how the plasma Zn pool influences endothelial intracellular labile Zn would be helpful in appreciating the importance of Zn deficiency in atherogenesis.

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

NARCIS (Netherlands)

Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an

Persistent diffuse pulmonary interstitial emphysema mimicking pulmonary emphysema

OpenAIRE

Demura, Y; Ishizaki, T; Nakanishi, M; Ameshima, S; Itoh, H

2009-01-01

A 69-year-old male non-smoker with a history of atopic asthma presented with symptoms suggestive of chronic obstructive pulmonary disease and this appeared to be corroborated by lung function testing and a chest radiograph. However, a chest CT showed no evidence of pulmonary emphysema and instead demonstrated free air along the bronchovascular sheaths indicative of pulmonary interstistial emphysema, possibly caused by repeated prior exacerbations of asthma. His lung function tests and symptom...

Optimizing computed tomography pulmonary angiography using right atrium bolus monitoring combined with spontaneous respiration

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Min, Wang; Jian, Li; Rui, Zhai [Jining No. 1 People' s Hospital, Department of Computed Tomography, Jining City, ShanDong Province (China); Wen, Li [Jining No. 1 People' s Hospital, Department of Gastroenterology, Jining, ShanDong (China); Dai, Lun-Hou [Shandong Chest Hospital, Department of Radiology, Jinan, ShanDong (China)

2015-09-15

CT pulmonary angiography (CTPA) aims to provide pulmonary arterial opacification in the absence of significant pulmonary venous filling. This requires accurate timing of the imaging acquisition to ensure synchronization with the peak pulmonary artery contrast concentration. This study was designed to test the utility of right atrium (RA) monitoring in ensuring optimal timing of CTPA acquisition. Sixty patients referred for CTPA were divided into two groups. Group A (n = 30): CTPA was performed using bolus triggering from the pulmonary trunk, suspended respiration and 70 ml of contrast agent (CA). Group B (n = 30): CTPA image acquisition was triggered using RA monitoring with spontaneous respiration and 40 ml of CA. Image quality was compared. Subjective image quality, average CT values of pulmonary arteries and density difference between artery and vein pairs were significantly higher whereas CT values of pulmonary veins were significantly lower in group B (all P < 0.05). There was no significant difference between the groups in the proportion of subjects where sixth grade pulmonary arteries were opacified (P > 0.05). RA monitoring combined with spontaneous respiration to trigger image acquisition in CTPA produces optimal contrast enhancement in pulmonary arterial structures with minimal venous filling even with reduced doses of CA. (orig.)

Balloon pulmonary angioplasty: a treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension

Directory of Open Access Journals (Sweden)

Aiko eOgawa

2015-02-01

Full Text Available In chronic thromboembolic pulmonary hypertension, stenoses or obstructions of the pulmonary arteries due to organized thrombi can cause an elevation in pulmonary artery resistance, which in turn can result in pulmonary hypertension. Chronic thromboembolic pulmonary hypertension can be cured surgically by pulmonary endarterectomy; however, patients deemed unsuitable for pulmonary endarterectomy due to lesion, advanced age, or comorbidities have a poor prognosis and limited treatment options. Recently, advances have been made in balloon pulmonary angioplasty for these patients, and this review highlights this recent progress.

Phase-contrast MR assessment of pulmonary venous blood flow in children with surgically repaired pulmonary veins

International Nuclear Information System (INIS)

Valsangiacomo, Emanuela R.; Yoo, Shi-Joon; Barrea, Catherine; Smallhorn, Jeffrey F.; Macgowan, Christopher K.; Coles, John G.

2003-01-01

Pulmonary venous (PV) obstruction may complicate surgical repair of PV abnormalities. By combining phase-contrast cine (PC) imaging and contrast-enhanced angiography, magnetic resonance (MR) imaging can provide physiological information complementing anatomical diagnosis. To compare the PV flow pattern observed after surgical repair of PV abnormalities with normal PV flow pattern and to investigate the changes occurring in the presence of PV stenosis by using PC MR in children. By using PC MR, PV flow was evaluated in 14 patients (3 months-14 years) who underwent surgical repair for PV abnormalities. Eleven children (8-18 years) were studied as normal controls. Peak flow velocities and patterns were compared among three groups: normal veins (n=23), surgically repaired veins without (n=44) and with stenosis (n=10). Normal and unobstructed pulmonary veins after surgery showed a biphasic or triphasic flow pattern with one or two systolic peaks and a diastolic peak. Unobstructed surgically repaired veins showed decreased peak systolic velocity (P =0.001) and an increased peak diastolic velocity (P=0.005) when compared to normal values. Obstructed veins showed decreased systolic and diastolic velocities when measured upstream from the stenosis. PC MR shows different flow patterns among normal, surgically repaired pulmonary veins with and without stenosis. (orig.)

Voluntary wheel running is beneficial to the amino acid profile of lysine-deficient rats.

Science.gov (United States)

Nagao, Kenji; Bannai, Makoto; Seki, Shinobu; Kawai, Nobuhiro; Mori, Masato; Takahashi, Michio

2010-06-01

Rats voluntarily run up to a dozen kilometers per night when their cages are equipped with a running wheel. Daily voluntary running is generally thought to enhance protein turnover. Thus, we sought to determine whether running worsens or improves protein degradation caused by a lysine-deficient diet and whether it changes the utilization of free amino acids released by proteolysis. Rats were fed a lysine-deficient diet and were given free access to a running wheel or remained sedentary (control) for 4 wk. Amino acid levels in plasma, muscle, and liver were measured together with plasma insulin levels and tissue weight. The lysine-deficient diet induced anorexia, skeletal muscle loss, and serine and threonine aminoacidemia, and it depleted plasma insulin and essential amino acids in skeletal muscle. Allowing rats to run voluntarily improved these symptoms; thus, voluntary wheel running made the rats less susceptible to dietary lysine deficiency. Amelioration of the declines in muscular leucine and plasma insulin observed in running rats could contribute to protein synthesis together with the enhanced availability of lysine and other essential amino acids in skeletal muscle. These results indicate that voluntary wheel running under lysine-deficient conditions does not enhance protein catabolism; on the contrary, it accelerates protein synthesis and contributes to the maintenance of muscle mass. The intense nocturnal voluntary running that characterizes rodents might be an adaptation of lysine-deficient grain eaters that allows them to maximize opportunities for food acquisition.

Pulmonary Hypertension Overview

Science.gov (United States)

... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

Familial Pulmonary Fibrosis

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... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

Solid lipid nanoparticles for pulmonary delivery of insulin.

Science.gov (United States)

Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

2008-05-22

Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

Experimental pulmonary carcinogenesis by radon and its daughters

International Nuclear Information System (INIS)

Sato, Fumiaki

1989-01-01

Information on experimental pulmonary carcinogenesis by radon and its daughters has come mostly from experiments carried out in France and United States of America. In rats a dose response relation was estimated to be linear with dose at low dose region. Studies of rats exposed daily to radon and radon daughters indicated that the frequency of pulmonary cancer at total exposure greater than 3000 WLM was greater when the exposure rates were low. At low total exposures the dose-rate effect was less apparent. Cigarette smoke increased the pulmonary cancer in rats but decreased in dogs. The decrease may be due to a decrease of absorbed doses with increased secretion of mucus and to an enhancement of mucociliary clearance. After inhalation of 222 Ru at equilibrium with radon daughters, rats were inoculated intrapleurally with asbestos fibres or glass fibres. The additive co-carcinogenic effects of this type of insult were demonstrated by the increased incidence of malignant thoracic tumours. As for species differences, dogs and hamsters are relatively resistant to cancer induction and rats are sensitive. While bronchogenic carcinomas are the most frequently observed radiation-induced pulmonary cancer in humans, bronchioloalveolar carcinomas are the most frequent type in most animal species. (author)

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

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Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

2007-11-01

Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSIA AT THE YOUNG PATIENT. CLINICAL OBSERVATION

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N. A. Kosheleva

2018-01-01

Full Text Available The work purpose — to describe a clinical case of formation and a current of a chronic thromboembolic pulmonary hypertensia (CTEPH at the patient of young age. Materials and methods. The patient P., 26 years, arrived with complaints to the dyspnea arising at rest and amplifying at the minimum exercise stress, edemas of the lower extremities. In the anamnesis — a clottage of subclavial and humeral veins on the right, recurrent PTE. Results. During inspection at the patient an echocardiography signs of a pulmonary hypertensia. According to contrast-enhanced multislice computed tomography in dynamics there was a dissolution of thrombs in a lumen of a pulmonary artery. At the patient data for a thrombophilia or a systemic vasculitis aren’t taped. Conclusion. In this clinical case features of a current and maintaining the patient of young age with CTEPH after the postponed PTE are displayed. The young age, idiopathic and recurrent character of a pulmonary embolism were the contributing risk factors of development of CTEPH. 

A comparative analysis of pulmonary ventilation-perfusion imaging with pulmonary angiography in the diagnosis of pulmonary embolism

International Nuclear Information System (INIS)

Wang Jincheng; Mi Hongzhi; Wang Qian; Zhang Weijun; Lu Biao; Yang Hao; Ding Jian; Lu Yao

2001-01-01

Objective: To assess the value of ventilation-perfusion imaging in the diagnosis of pulmonary embolism (PE). Methods: Thirty consecutive patients with clinically suspected pulmonary embolism were studied, male: female 15:15, mean age was (36.2 +- 13.9) years. The chest radiograms were obtained in all 30 patients. All patients underwent radionuclide ventilation-perfusion imaging and pulmonary angiography. Results: Of the 30 patients, 22 with lobe, multiple segment or multi-subsegment perfusion defects and normal or nearly normal ventilation images were reported as PE. 20 of them were confirmed to be with PE by pulmonary angiography, 2 patients were not confirmed. Eight of 30 patients with multiple perfusion defects, ventilative abnormalities were reported as non-PE and the diagnoses were confirmed by pulmonary angiography. The sensitivity, specificity and accuracy of diagnosis of PE by ventilation-perfusion imaging was 100%, 80.0% and 93.3% respectively. Conclusions: (1) Ventilation-perfusion imaging is one of the most valuable methods in the diagnosis of PE. (2) The results suggest that pulmonary embolism can be diagnosed non-invasively in most patients on the basis of clinical manifestation, chest radiograms and ventilation-perfusion imaging findings. (3) Pulmonary angiography is required while clinical manifestation and ventilation-perfusion imaging findings are discordant with each other

Dynamic computed tomography findings of atypical pulmonary hamartoma and it's pathologic correlations: A case report

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Hong, Seung Baek; Jeong Yeon Joo Lee, Gee Won; Kim, Yeong Dae; Ahn, Hyo Yeong; Lee, Chang Hoon; Kim, Ah Rong; Lee, Ji Won [Medical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

2016-04-15

We present the dynamic contrast-enhanced computed tomography (CT) findings of atypical pulmonary hamartoma with a rare histologic pattern in a 20-year-old male. CT showed a 3.4 cm lobulated mass with a 'tip of the iceberg' appearance in the medium bronchus of the right lower lobe. Dynamic contrast-enhanced CT demonstrated a heterogeneously and persistently enhancing mass. The CT Hounsfield unit (HU) measurements were: 17 HU pre-contrast, 32 HU at 1 minute, 44 HU at 2 minutes, 51 HU at 4 minutes, and 64 HU at 15 minutes. Pathologic examination after video-assisted thoracoscopic surgery disclosed a pulmonary hamartoma with a predominant fibroblastic component.

Diagnostic accuracy of unenhanced, contrast-enhanced perfusion and angiographic MRI sequences for pulmonary embolism diagnosis: results of independent sequence readings

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Revel, Marie Pierre [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Hotel-Dieu, Service de Radiologie, Paris (France); Sanchez, Olivier; Meyer, Guy [Hopital Europeen Georges Pompidou, APHP, Respiratory and intensive care and, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM Unite 765, Paris (France); Lefort, Catherine; Couchon, Sophie; Hernigou, Anne; Frija, Guy [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Niarra, Ralph [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Chatellier, Gilles [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM CIC-EC E4, Paris (France)

2013-09-15

To independently evaluate unenhanced, contrast-enhanced perfusion and angiographic MR sequences for pulmonary embolism (PE) diagnosis. Prospective investigation, including 274 patients who underwent perfusion, unenhanced 2D steady-state-free-precession (SSFP) and contrast-enhanced 3D angiographic MR sequences on a 1.5-T unit, in addition to CTA (CT angiography). Two independent readers evaluated each sequence independently in random order. Sensitivity, specificity, predictive values and inter-reader agreement were calculated for each sequence, excluding sequences judged inconclusive. Sensitivity was also calculated according to PE location. Contrast-enhanced angiographic sequences showed the highest sensitivity (82.9 and 89.7 %, reader 1 and reader 2, respectively), specificity (98.5 and 100 %) and agreement (kappa value 0.77). Unenhanced angiographic sequences, although less sensitive overall (68.7 and 76.4 %), were sensitive for the detection of proximal PE (92.7 and 100 %) and showed high specificity (96.1 and 99.1 %) and good agreement (kappa value 0.62). Perfusion sequences showed lower sensitivity (75.0 and 79.3 %), specificity (84.8 and 89.7 %) and agreement (kappa value 0.51), and a negative predictive value of 84.8 % at best. Compared with contrast-enhanced angiographic sequences, unenhanced sequences demonstrate lower sensitivity, except for proximal PE, but high specificity and agreement. The negative predictive value of perfusion sequences was insufficient to safely rule out PE. (orig.)

Recent advances in understanding and treating COPD related to α1-antitrypsin deficiency.

Science.gov (United States)

Henao, Maria Paula; Craig, Timothy J

2016-12-01

Alpha-1-antitrypsin deficiency (AATD) is an orphan disease that predisposes individuals to COPD and liver disease. The following is a comprehensive review of AATD from epidemiology to treatment for physicians who treat COPD or asthma. Areas covered: In this comprehensive review of alpha-1-antitrypsin deficiency, we describe the historical perspective, genetics, epidemiology, clinical presentation and symptoms, screening and diagnosis, and treatments of the condition. Expert commentary: The two most important directions for advancing the understanding of AATD involve improving detection of the condition, especially in asymptomatic patients, and advancing knowledge of treatments directed specifically at AATD-related conditions. With regard to treatment for AATD-related conditions, research must continue to explore the implications and importance of augmentation therapy as well as consider new implementations that may prove more successful taking into consideration not only factors of pulmonary function and liver health, but also product availability and financial viability.

Right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus

International Nuclear Information System (INIS)

Lee, Peter; McCauley, Roy; Westra, Sjirk; Baba, Timothy

2006-01-01

Pulmonary aplasia and bronchopulmonary foregut malformations in which a patent communication between the foregut and the pulmonary system is present are rare congenital abnormalities. Pulmonary aplasia associated with a pulmonary sling is an even rarer abnormality. We report a unique case of right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus diagnosed by multidetector helical CT. (orig.)

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins

NARCIS (Netherlands)

Szafranski, P.; Gambin, T.; Dharmadhikari, A.V.; Akdemir, K.C.; Jhangiani, S.N.; Schuette, J.; Godiwala, N.; Yatsenko, S.A.; Sebastian, J.; Madan-Khetarpal, S.; Surti, U.; Abellar, R.G.; Bateman, D.A.; Wilson, A.L.; Markham, M.H.; Slamon, J.; Santos-Simarro, F.; Palomares, M.; Nevado, J.; Lapunzina, P.; Chung, B.H.; Wong, W.L.; Chu, Y.W.; Mok, G.T.; Kerem, E.; Reiter, J.; Ambalavanan, N.; Anderson, S.A.; Kelly, D.R.; Shieh, J.; Rosenthal, T.C.; Scheible, K.; Steiner, L.; Iqbal, M.A.; McKinnon, M.L.; Hamilton, S.J.; Schlade-Bartusiak, K.; English, D.; Hendson, G.; Roeder, E.R.; DeNapoli, T.S.; Littlejohn, R.O.; Wolff, D.J.; Wagner, C.L.; Yeung, A.; Francis, D.; Fiorino, E.K.; Edelman, M.; Fox, J.; Hayes, D.A.; Janssens, S.; Baere, E. De; Menten, B.; Loccufier, A.; Vanwalleghem, L.; Moerman, P.; Sznajer, Y.; Lay, A.S.; Kussmann, J.L.; Chawla, J.; Payton, D.J.; Phillips, G.E.; Brosens, E.; Tibboel, D.; Klein, A.; Maystadt, I.; Fisher, R.; Sebire, N.; Male, A.; Chopra, M.; Pinner, J.; Malcolm, G.; Peters, G.; Arbuckle, S.; Lees, M.; Mead, Z.; Quarrell, O.; Sayers, R.; Owens, M.; Shaw-Smith, C.; Lioy, J.; McKay, E.; Leeuw, N. de; Feenstra, I.; Spruijt, L.; Elmslie, F.; Thiruchelvam, T.; Bacino, C.A.; Langston, C.; Lupski, J.R.; Sen, P.; Popek, E.; Stankiewicz, P.

2016-01-01

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes

Radiation enhances silica translocation to the pulmonary interstitium and increases fibrosis in mice

International Nuclear Information System (INIS)

Adamson, I.Y.R.

1992-01-01

The effects of whole body irradiation (WBR) on particle clearance and the development of pulmonary fibrosis have been investigated. Using carbon, clearance is accomplished by polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM), and only a few particles reach the interstitum. However, in preirradiated mice, the usual eflux of inflammatory cells is much delayed so that more free carbon remains in the alveoli, and by 1 week, many particles cross the epithelium to be phagocytized by interstitial macrophages. Carbon is found in the peribronchiolar interstitium 6 months later with no evidence of fibrosis. In the present study, mice received 1 mg silica intratracheally 2 days after 6.5 Gy WBR when the white blood cell count was low. A much-reduced Am and PMN response was found in the following 2 weeks compared to the reaction to silica alone, and many silica particles reached interstitial macrophages. In this case, macrophage activation by silica was associated with fibroblast proliferation, and by 16 weeks, much more pulmonary fibrosis was produced than after silica or irradiation only. This was measured biochemically and correlated with a large increase in retained silica in the irradiation-silica group. The results indicate that radiation inhibits the inflammatory response to particle instillation, resulting in greater translocation of free particles to the pulmonary interstitium. In the case of silica, the greater, prolonged interaction with interstitial macrophages leads to a much exaggerated fibrotic reaction. 17 refs., 11 figs

Oxygen enhancement ratios for glutathione-deficient human fibroblasts determined from the frequency of radiation induced micronuclei

International Nuclear Information System (INIS)

Midander, J.

1982-01-01

The yield of micronuclei (MN) was determined to study the radiosensitizing effect of oxygen on three human fibroblast strains, characterized by genetically defined differences in their glutathione (GSH) level. Cells were irradiated in paired experiments with x-ray doses of 2.66 and 6.65 gy in their exponential growth phase in a monolayer under oxic and anoxic conditions. Results indicated a reduced oxygen effect for the GSH deficient cells, the reduction of o.e.r. being most pronounced in the case of GSHsup(-/-) cells, when it was close to unity. The o.e.r. value was intermediate for the GSHsup(+/-) in comparison with the two other cell strains. It is concluded that the data indicate a correlation between the cellular content of GSH and the oxygen enhancement of the formation of micronuclei after irradiation. (U.K.)

Mice lacking cystathionine beta synthase have lung fibrosis and air space enlargement.

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Hamelet, Julien; Maurin, Nicole; Fulchiron, Romain; Delabar, Jean-Maurice; Janel, Nathalie

2007-10-01

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations, notably pulmonary thrombotic disease. However, the association between hyperhomocysteinemia and chronic obstructive pulmonary disease is not well understood. To investigate the role of hyperhomocysteinemia in lung injury and pulmonary fibrosis, we analyzed the lung of CBS-deficient mice, a murine model of severe hyperhomocysteinemia. The degree of lung injury was assessed by histologic examination. Analysis of profibrogenic factors was performed by real-time quantitative reverse transcription-polymerase chain reaction. CBS-deficient mice develop fibrosis and air space enlargement in the lung, concomitant with an enhanced expression of heme oxygenase-1, pro(alpha)1 collagen type I, transforming growth factor-beta1 and alpha-smooth muscle actin. However, lung fibrosis was found in the absence of increased inflammatory cell infiltrates as determined by histology, without changes in gene expression of proinflammatory cytokines TNFalpha and interleukin 6. The increased expression of alpha-smooth muscle actin and transforming growth factor-beta1 emphasizes the role of myofibroblasts differentiation in case of lung fibrosis due to CBS deficiency in mice.

Pulmonary Arterial Hypertension

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... heart). This type of pulmonary hypertension was called “secondary pulmonary hypertension” but is now referred to as PH, because the cause is known to be from lung disease, heart disease, or chronic thromboemboli (blood clots). Pulmonary Arterial Hypertension (PAH) used to be ...

Progenitor cells in pulmonary vascular remodeling

Science.gov (United States)

Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

2011-01-01

Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

Oxygen-enhanced magnetic resonance ventilation imaging of lung

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Chen Qun; Hatabu, Hiroto

2001-01-01

The oxygen-enhanced magnetic resonance (MR) ventilation imaging is a new technique, and the full extent of its physiological significance has not been elucidated. This review article includes background on (1) respiratory physiology; (2) mechanism and optimization of oxygen-enhanced MR imaging technique; (3) recent applications in animal and human models; and (4) merits and demerits of the technique in comparison with hyperpolarized noble gas MR ventilation imaging. Application of oxygen-enhanced MR ventilation imaging to patients with pulmonary diseases has been very limited. However, we believe that further basic studies, as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR ventilation imaging in the future of pulmonary functional imaging and its usefulness for diagnostic radiology

Pulmonary vascular limitation to exercise and survival in idiopathic pulmonary fibrosis

NARCIS (Netherlands)

van der Plas, Mart N.; van Kan, Coen; Blumenthal, Judith; Jansen, Henk M.; Wells, Athol U.; Bresser, Paul

2014-01-01

Pulmonary hypertension is frequently observed in advanced idiopathic pulmonary fibrosis (IPF) and is associated with poor prognosis. Cardiopulmonary exercise testing (CPET) can be used to detect less advanced pulmonary vascular impairment, and therefore may be of prognostic use. We studied the

Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair.

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Löser, Dana A; Shibata, Atsushi; Shibata, Akiko K; Woodbine, Lisa J; Jeggo, Penny A; Chalmers, Anthony J

2010-06-01

As single agents, chemical inhibitors of poly(ADP-ribose) polymerase (PARP) are nontoxic and have clinical efficacy against BRCA1- and BRCA2-deficient tumors. PARP inhibitors also enhance the cytotoxicity of ionizing radiation and alkylating agents but will only improve clinical outcomes if tumor sensitization exceeds effects on normal tissues. It is unclear how tumor DNA repair proficiency affects the degree of sensitization. We have previously shown that the radiosensitizing effect of PARP inhibition requires DNA replication and will therefore affect rapidly proliferating tumors more than normal tissues. Because many tumors exhibit defective DNA repair, we investigated the impact of double-strand break (DSB) repair integrity on the sensitizing effects of the PARP inhibitor olaparib. Sensitization to ionizing radiation and the alkylating agent methylmethane sulfonate was enhanced in DSB repair-deficient cells. In Artemis(-/-) and ATM(-/-) mouse embryo fibroblasts, sensitization was replication dependent and associated with defective repair of replication-associated damage. Radiosensitization of Ligase IV(-/-) mouse embryo fibroblasts was independent of DNA replication and is explained by inhibition of "alternative" end joining. After methylmethane sulfonate treatment, PARP inhibition promoted replication-independent accumulation of DSB, repair of which required Ligase IV. Our findings predict that the sensitizing effects of PARP inhibitors will be more pronounced in rapidly dividing and/or DNA repair defective tumors than normal tissues and show their potential to enhance the therapeutic ratio achieved by conventional DNA-damaging agents.

Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension

Directory of Open Access Journals (Sweden)

David Jenkins

2017-03-01

Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a type of pulmonary hypertension, resulting from fibrotic transformation of pulmonary artery clots causing chronic obstruction in macroscopic pulmonary arteries and associated vascular remodelling in the microvasculature. Pulmonary endarterectomy (PEA offers the best chance of symptomatic and prognostic improvement in eligible patients; in expert centres, it has excellent results. Current in-hospital mortality rates are 90% at 1 year and >70% at 10 years. However, PEA, is a complex procedure and relies on a multidisciplinary CTEPH team led by an experienced surgeon to decide on an individual's operability, which is determined primarily by lesion location and the haemodynamic parameters. Therefore, treatment of patients with CTEPH depends largely on subjective judgements of eligibility for surgery by the CTEPH team. Other controversies discussed in this article include eligibility for PEA versus balloon pulmonary angioplasty, the new treatment algorithm in the European Society of Cardiology/European Respiratory Society guidelines and the definition of an “expert centre” for the management of this condition.

[Paradoxical brain embolism mediated through a pulmonary arteriovenous malformation with hereditary hemorrhagic telangiectasia in a Japanese patient].

Science.gov (United States)

Takeda, June; Todo, Kenichi; Yamamoto, Shiro; Yamagami, Hiroshi; Kawamoto, Michi; Kohara, Nobuo

2012-01-01

We report a case of paradoxical brain embolism mediated through a pulmonary arteriovenous malformation (PAVM) with hereditary hemorrhagic telangiectasia (HHT). A 25-year-old right handed man was admitted to our hospital after sudden headache and visual field abnormality. In neurologic examinations, he had left superior-quadrantanopsia. Laboratory findings showed iron deficiency anemia. Diffusion weighted images disclosed a high-signal-intensity area in the right occipito-temporal lobe, and intraarterial digital subtraction cerebral angiography revealed occlusion of the right posterior cerebral artery. Transesophageal echocardiography revealed continuous right-to-left shunt. We confirmed his history of spontaneous recurrent epistaxis and the first-degree relatives with epistaxis or PAVM. A contrast enhanced CT scan of the chest revealed a PAVM. The diagnosis of paradoxical brain embolism mediated through the PAVM with HHT was, thus, established. The PAVM was occluded by using embolization coils successfully. In Asian countries, the prevalence of PAVM with HHT is thought to be lower than in European countries. We should carefully take medical and family histories, especially epistaxis, in a young stroke patient.

Does exercise pulmonary hypertension exist?

Science.gov (United States)

Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

2016-09-01

The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

Iodine Deficiency

Science.gov (United States)

... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

Definition and classification of pulmonary hypertension.

Science.gov (United States)

Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

2013-01-01

Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

Pulmonary vascular imaging

International Nuclear Information System (INIS)

Fedullo, P.F.; Shure, D.

1987-01-01

A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

Micronutrient deficiencies and gender: social and economic costs.

Science.gov (United States)

Darnton-Hill, Ian; Webb, Patrick; Harvey, Philip W J; Hunt, Joseph M; Dalmiya, Nita; Chopra, Mickey; Ball, Madeleine J; Bloem, Martin W; de Benoist, Bruno

2005-05-01

Vitamin and mineral deficiencies adversely affect a third of the world's people. Consequently, a series of global goals and a serious amount of donor and national resources have been directed at such micronutrient deficiencies. Drawing on the extensive experience of the authors in a variety of institutional settings, the article used a computer search of the published scientific literature of the topic, supplemented by reports and published and unpublished work from the various agencies. In examining the effect of sex on the economic and social costs of micronutrient deficiencies, the paper found that: (1) micronutrient deficiencies affect global health outcomes; (2) micronutrient deficiencies incur substantial economic costs; (3) health and nutrition outcomes are affected by sex; (4) micronutrient deficiencies are affected by sex, but this is often culturally specific; and finally, (5) the social and economic costs of micronutrient deficiencies, with particular reference to women and female adolescents and children, are likely to be considerable but are not well quantified. Given the potential impact on reducing infant and child mortality, reducing maternal mortality, and enhancing neuro-intellectual development and growth, the right of women and children to adequate food and nutrition should more explicitly reflect their special requirements in terms of micronutrients. The positive impact of alleviating micronutrient malnutrition on physical activity, education and productivity, and hence on national economies suggests that there is also an urgent need for increased effort to demonstrate the cost of these deficiencies, as well as the benefits of addressing them, especially compared with other health and nutrition interventions.

Xenon-enhanced CT using subtraction CT: Basic and preliminary clinical studies for comparison of its efficacy with that of dual-energy CT and ventilation SPECT/CT to assess regional ventilation and pulmonary functional loss in smokers

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Yoshikawa, Takeshi; Takenaka, Daisuke; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Sugimura, Kazuro

2017-01-01

Purpose: To prospectively and directly compare the capability for assessments of regional ventilation and pulmonary functional loss in smokers of xenon-ventilation CT obtained with the dual-energy CT (DE-CT) and subtraction CT (Sub-CT) Materials and methods: Twenty-three consecutive smokers (15 men and 8 women, mean age: 69.7 ± 8.7 years) underwent prospective unenhanced and xenon-enhanced CTs, the latter by Sub-CT and DE-CT methods, ventilation SPECT and pulmonary function tests. Sub-CT was generated from unenhanced and xenon-enhanced CT, and all co-registered SPECT/CT data were produced from SPECT and unenhanced CT data. For each method, regional ventilation was assessed by using a 11-point scoring system on a per-lobe basis. To determine the functional lung volume by each method, it was also calculated for individual sublets with a previously reported method. To determine inter-observer agreement for each method, ventilation defect assessment was evaluated by using the χ2 test with weighted kappa statistics. For evaluation of the efficacy of each method for pulmonary functional loss assessment, functional lung volume was correlated with%FEV 1 . Results: Each inter-observer agreement was rated as substantial (Sub-CT: κ = 0.69, p < 0.0001; DE-CT: κ = 0.64, p < 0.0001; SPECT/CT: κ = 0.64, p < 0.0001). Functional lung volume for each method showed significant to good correlation with%FEV 1 (Sub-CT: r = 0.72, p = 0.0001; DE-CT: r = 0.74, p < 0.0001; SPECT/CT: r = 0.66, p = 0.0006). Conclusion: Xenon-enhanced CT obtained by Sub-CT can be considered at least as efficacious as that obtained by DE-CT and SPECT/CT for assessment of ventilation abnormality and pulmonary functional loss in smokers.

Xenon-enhanced CT using subtraction CT: Basic and preliminary clinical studies for comparison of its efficacy with that of dual-energy CT and ventilation SPECT/CT to assess regional ventilation and pulmonary functional loss in smokers

Energy Technology Data Exchange (ETDEWEB)

Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan); Yoshikawa, Takeshi [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan); Takenaka, Daisuke [Department of Radiology, Hyogo Cancer Center, Akashi (Japan); Fujisawa, Yasuko; Sugihara, Naoki [Toshiba Medical Systems Corporation, Otawara (Japan); Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine (Japan)

2017-01-15

Purpose: To prospectively and directly compare the capability for assessments of regional ventilation and pulmonary functional loss in smokers of xenon-ventilation CT obtained with the dual-energy CT (DE-CT) and subtraction CT (Sub-CT) Materials and methods: Twenty-three consecutive smokers (15 men and 8 women, mean age: 69.7 ± 8.7 years) underwent prospective unenhanced and xenon-enhanced CTs, the latter by Sub-CT and DE-CT methods, ventilation SPECT and pulmonary function tests. Sub-CT was generated from unenhanced and xenon-enhanced CT, and all co-registered SPECT/CT data were produced from SPECT and unenhanced CT data. For each method, regional ventilation was assessed by using a 11-point scoring system on a per-lobe basis. To determine the functional lung volume by each method, it was also calculated for individual sublets with a previously reported method. To determine inter-observer agreement for each method, ventilation defect assessment was evaluated by using the χ2 test with weighted kappa statistics. For evaluation of the efficacy of each method for pulmonary functional loss assessment, functional lung volume was correlated with%FEV{sub 1}. Results: Each inter-observer agreement was rated as substantial (Sub-CT: κ = 0.69, p < 0.0001; DE-CT: κ = 0.64, p < 0.0001; SPECT/CT: κ = 0.64, p < 0.0001). Functional lung volume for each method showed significant to good correlation with%FEV{sub 1} (Sub-CT: r = 0.72, p = 0.0001; DE-CT: r = 0.74, p < 0.0001; SPECT/CT: r = 0.66, p = 0.0006). Conclusion: Xenon-enhanced CT obtained by Sub-CT can be considered at least as efficacious as that obtained by DE-CT and SPECT/CT for assessment of ventilation abnormality and pulmonary functional loss in smokers.

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

Science.gov (United States)

Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

A study on the pulmonary mean transit time and the pulmonary blood volume by RI-cardiogram

International Nuclear Information System (INIS)

Ushio, Norio

1987-01-01

The pulmonary mean transit time and the pulmonary blood volume in cases of cardio-pulmonary disease were measured using Giuntini's method which is considered the most appropriate among radiocardiographic methods. The errors in this method were confirmed to be almost negligible. The results obtained were as follows: 1) The pulmonary mean transit time was related to the systemic mean transit time and markedly prolonged in left heart failure. On the other hand, it was markedly shortened in some cases of chronic pulmonary disease, particularly pulmonary emphysema. 2) The pulmonary blood volume tended to increase in left heart disorders and mitral valve disease and tended to decrease in the chronic pulmonary disease. The decrease was conspicuous particularly in some cases of pulmonary emphysema. 3) A structural change of the pulmonary vascular system in the chronic pulmonary disease appeared to bring about shortening of the pulmonary mean transit time and a decrease in the pulmonary blood volume. The pathophysiology of cardio-pulmonary disease can be more clarified by the RI-cardiogram used in this study, in which the pulmonary mean transit time and the pulmonary blood volume are used as the indicator. (author)

Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

Directory of Open Access Journals (Sweden)

Weissmann Norbert

2005-07-01

Full Text Available Abstract Inhaled prostanoids and phosphodiesterase (PDE inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor, motapizone (PDE3 inhibitor or 8-Methoxymethyl-IBMX (PDE1 inhibitor synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.

Neuropsychological dysfunction in patients suffering from end-stage chronic obstructive pulmonary disease

Science.gov (United States)

Crews, W. David; Jefferson, Angela L.; Bolduc, Tara; Elliott, Jennifer B.; Ferro, Nikola M.; Broshek, Donna K.; Barth, Jeffrey T.; Robbins, Mark K.

2009-01-01

Few studies have examined the neuropsychological sequelae associated with end-stage pulmonary disease. Neuropsychological data are presented for 47 patients with end-stage chronic obstructive pulmonary disease (COPD) who were being evaluated as potential candidates for lung transplantation. Although patients exhibited a diversity of neurocognitive deficits, their highest frequencies of impairment were found on the Selective Reminding Test (SRT). Specifically, over 50% of the patients completing the SRT exhibited impaired immediate free recall and consistent long-term retrieval deficits, while more than 44% of these individuals displayed deficient long-term retrieval. Deficient SRT long-term storage strategies, cued recall, and delayed recall were exhibited by between 26% and 35% of these patients, while more than 32% of this sample displayed elevated numbers of intrusion errors. Over 31% of the patients completing the Wisconsin Card Sorting Test (WCST) failed to achieve the expected number of categories on this measure, while more than 23% of these individuals demonstrated elevated numbers of perseverative errors and total errors. Clinically notable frequencies of impairment (greater than 20% of the sample) were also found on the Trail Making Test (TMT): Part B and the Wechsler Memory Scale-R (WMS-R) Visual Reproduction II subtest. Minnesota Multiphasic Personality Inventory-2 (MMPI-2) personality assessments indicated that patients were experiencing a diversity of somatic complaints and that they may have been functioning at a reduced level of efficiency. These findings are discussed in light of patients’ end-stage COPD and factors possibly contributing to their neuropsychological test performances. Implications for clinical practice and future research are also included. PMID:14589783

The comparison of CT findings between peripheral pulmonary squamous cell carcinoma and pulmonary adenocarcinoma

International Nuclear Information System (INIS)

Tan Guosheng; Yang Xufeng; Zhou Xuhui; Li Ziping; Fan Miao; Chen Jindi

2007-01-01

Objective: To compare the principal HRCT features of peripheral pulmonary squamous cell carcinoma and pulmonary adenocarcinoma and to explore their pathological mechanism, in order to improve the recognition of the CT signs of peripheral pulmonary carcinoma. Methods: The principal HRCT signs of thirty-five cases with pathologically proved peripheral pulmonary squamous cell carcinoma and forty cases with pathologically proved peripheral pulmonary adenocarcinoma were analyzed retrospectively to explore the relationship between CT features and pathological findings. Results: The main features of peripheral pulmonary squamous cell carcinoma included larger masses, clear boundary, superficial sublobes and intra-tumor necrosis. While peripheral pulmonary adenocarcinoma mostly demonstrated as smaller nodules, deep sublobes, spiculations, spiculate protuberance, pleural indentation, vessel converging signs, and vacuole signs. The different of these above findings of peripheral pulmonary squamous cell carcinoma and adenocarcinoma were significant (P<0.05). Peripheral pulmonary squamous cell carcinoma may depict bronchial casts and polygonal nodules; and peripheral pulmonary adenocarcinoma may demonstrate ground glass-like nodules. Conclusion: The difference of the CT findings between peripheral pulmonary squamous cell carcinoma and peripheral adenocarcinoma is based on their different histological features and biological behaviors. It is possible to differentiate them before operation in combination with clinical information. (authors)

Pulmonary arterial hypertension : an update

NARCIS (Netherlands)

Hoendermis, E. S.

2011-01-01

Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

Correlation between CT review findings and pulmonary function in pulmonary emphysema

International Nuclear Information System (INIS)

Inoue, Masaki; Fukuda, Kiyoshi; Homma, Toshiaki

1987-01-01

We investigated the correlation between CT and pulmonary function test results in five normal controls and ten patients with severe pulmonary emphysema. We used mean lung attenuation values (MLAV) and ΔEMP as the index of emphysematous change in CT. ΔEMP was defined as the ratio of the area (-960 Hounsfield Units ∼ -1024 HU) to the area (-774 HU ∼ -1024 HU). MLAV and ΔEMP were measured from histograms of the CT review. Mean MLAV in pulmonary emphysema was -947.1 ± 9.3 HU, and that in normal controls was -906.6 ± 23.6 HU. Mean ΔEMP in pulmonary emphysema was 50.0 ± 9.9 %, and that in normal controls was 18.8 ± 13.0 %. The data in pulmonary emphysema cases differed significantly from those in normal controls. Furthermore MLAV and ΔEMP had good correlation to VC, %VC, FEV 1 , FEV 1 /FVC, RV/TLC, %V 25 and Raw. CT is an easier examination than pulmonary function test for patients, and can show the extent and the distribution of emphysematous area. In this study it is suggested that CT is a useful examination in severe pulmonary emphysema. (author)

Effects of irradiation on the pulmonary hemodynamics and the pulmonary vascular permeability

International Nuclear Information System (INIS)

Ohkuda, Kazuhiro; Watanabe, Shinkichi; Okada, Shinichiroh

1982-01-01

In 4 sheeps, base lines of hemodynamics and lymph dynamics were observed for 2 hours, and then 1,000 rad of 60 Co was irradiated to the inferior lobes of the lung. Pulmonary hemodynamics and lymph dynamics were continuously observed, and water and protein permeability of the irradiated pulmonary vessels was evaluated. In 4 control sheeps, no change in pulmonary hemodynamics and lymph dynamics was noted. In the irradiated group, there was no remarkable change in pulmonary hemodynamics for 6 to 8 hours after 60 Co irradiation. Pulmonary lymph flow began to increase 2 hours after irradiation to about 1.7 times the base line level after 4 hours. The increase in pulmonary lymph flow was accompanied by decrease in plasma protein concentration and increase in protein concentration of the lung lymph, resulting in an apparent increase in the ratio of lymph/plasma protein concentration. Water and protein leak from the pulmonary vessels increased. A photomicroscopic observation revealed dilatation of the lymphatic vessels in the lung interstice and a mild pulmonary interstitial edema. Vascular damage, especially due to increased water and protein permeability of the lung capillary vessels, occurred immediately after 60 Co irradiation. (Ueda, J.)

Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

DEFF Research Database (Denmark)

Li, Ying; Han, Meihua; Liu, Tingting

2017-01-01

The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...

Wedge and subselective pulmonary angiography in pulmonary hypertension secondary to venous obstruction

International Nuclear Information System (INIS)

Bowen, J.S.; Bookstein, J.J.; Johnson, A.D.; Peterson, K.L.; Moser, K.M.

1985-01-01

Pulmonary wedge or subselective angiography provided key diagnostic information in two cases of pulmonary hypertension secondary to pulmonary venous obstruction. Whereas conventional pulmonary angiograms and ventilation-perfusion lung scans were interpreted as showing embolism, plain radiographs demonstrated Kerley B lines, suggesting venous obstruction. Subselective or wedge angiography of nonopacified arteries verified their anatomical patency and also revealed venous stenoses, collaterals, and atrophy indicative of obstruction

TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

International Nuclear Information System (INIS)

Yan, Jidong; Xu, Jing; Fei, Yao; Jiang, Congshan; Zhu, Wenhua; Han, Yan; Lu, Shemin

2016-01-01

Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

Energy Technology Data Exchange (ETDEWEB)

Yan, Jidong [Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Xu, Jing [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Fei, Yao [College of Life Sciences, Northwest University, Xi’an, Shaanxi Province 710069 (China); Jiang, Congshan; Zhu, Wenhua; Han, Yan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Lu, Shemin, E-mail: lushemin@xjtu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China (China)

2016-05-15

Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

Directory of Open Access Journals (Sweden)

Jonghan Kim

Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Intravascular pulmonary metastases

International Nuclear Information System (INIS)

Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

1988-01-01

The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

Science.gov (United States)

Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

2012-01-01

The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism.

Science.gov (United States)

Pesavento, Raffaele; Filippi, Lucia; Palla, Antonio; Visonà, Adriana; Bova, Carlo; Marzolo, Marco; Porro, Fernando; Villalta, Sabina; Ciammaichella, Maurizio; Bucherini, Eugenio; Nante, Giovanni; Battistelli, Sandra; Muiesan, Maria Lorenza; Beltramello, Giampietro; Prisco, Domenico; Casazza, Franco; Ageno, Walter; Palareti, Gualtiero; Quintavalla, Roberto; Monti, Simonetta; Mumoli, Nicola; Zanatta, Nello; Cappelli, Roberto; Cattaneo, Marco; Moretti, Valentino; Corà, Francesco; Bazzan, Mario; Ghirarduzzi, Angelo; Frigo, Anna Chiara; Miniati, Massimo; Prandoni, Paolo

2017-05-01

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension. Copyright ©ERS 2017.

P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

Science.gov (United States)

Müller, Tobias; Fay, Susanne; Vieira, Rodolfo Paula; Karmouty-Quintana, Harry; Cicko, Sanja; Ayata, Cemil Korcan; Zissel, Gernot; Goldmann, Torsten; Lungarella, Giuseppe; Ferrari, Davide; Di Virgilio, Francesco; Robaye, Bernard; Boeynaems, Jean-Marie; Lazarowski, Eduardo R.; Blackburn, Michael R.; Idzko, Marco

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF. PMID:28878780

P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

Directory of Open Access Journals (Sweden)

Tobias Müller

2017-08-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF.

Transit of micro-bubbles through the pulmonary circulation of Thoroughbred horses during exercise.

Science.gov (United States)

La Gerche, A; Daffy, J R; Mooney, D J; Forbes, G; Davie, A J

2013-10-01

It has been observed that microbubbles may pass through the pulmonary circulation of dogs and humans during exercise. In humans, this phenomenon has been associated with lower pulmonary artery pressures, enhanced right ventricular function and greater exercise capacity. In the exercising Thoroughbred horse, extraordinarily high cardiac outputs exert significant pulmonary vascular stresses. The aim of this study was to determine, using contrast echocardiography, whether Thoroughbred horses performing strenuous exercise developed pulmonary transit of agitated contrast microbubbles (PTAC). At rest, agitated contrast was observed in the right ventricle, but not in the left ventricle. However, post-exercise microbubbles were observed in the left ventricle, confirming the occurrence of PTAC with exercise but not at rest. Further investigation is warranted to investigate whether this phenomenon may be associated with superior physiology and performance measures as has been implicated in other species. Copyright © 2013 Elsevier Ltd. All rights reserved.

Usability of Computerized Lung Auscultation-Sound Software (CLASS) for learning pulmonary auscultation.

Science.gov (United States)

Machado, Ana; Oliveira, Ana; Jácome, Cristina; Pereira, Marco; Moreira, José; Rodrigues, João; Aparício, José; Jesus, Luis M T; Marques, Alda

2018-04-01

The mastering of pulmonary auscultation requires complex acoustic skills. Computer-assisted learning tools (CALTs) have potential to enhance the learning of these skills; however, few have been developed for this purpose and do not integrate all the required features. Thus, this study aimed to assess the usability of a new CALT for learning pulmonary auscultation. Computerized Lung Auscultation-Sound Software (CLASS) usability was assessed by eight physiotherapy students using computer screen recordings, think-aloud reports, and facial expressions. Time spent in each task, frequency of messages and facial expressions, number of clicks and problems reported were counted. The timelines of the three methods used were matched/synchronized and analyzed. The tasks exercises and annotation of respiratory sounds were the ones requiring more clicks (median 132, interquartile range [23-157]; 93 [53-155]; 91 [65-104], respectively) and where most errors (19; 37; 15%, respectively) and problems (n = 7; 6; 3, respectively) were reported. Each participant reported a median of 6 problems, with a total of 14 different problems found, mainly related with CLASS functionalities (50%). Smile was the only facial expression presented in all tasks (n = 54). CLASS is the only CALT available that meets all the required features for learning pulmonary auscultation. The combination of the three usability methods identified advantages/disadvantages of CLASS and offered guidance for future developments, namely in annotations and exercises. This will allow the improvement of CLASS and enhance students' activities for learning pulmonary auscultation skills.

Clinical and Molecular Heterogeneity of RTEL1 Deficiency

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Marcin W. Wlodarski

2017-05-01

Full Text Available Typical features of dyskeratosis congenita (DC resulting from excessive telomere shortening include bone marrow failure (BMF, mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys, p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel heterozygous mutation p.Val796AlafsX4. The most unifying features were hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition, three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous recombination defect was detected in patient-derived fibroblasts but not in hematopoietic compartment. Notably, in both cellular compartments, differential expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts, response to ionizing irradiation and non-homologous end joining were not impaired. Telomeric circles did not accumulate in patient-derived primary cells and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative exhaustion, spontaneous apoptosis and senescence. Specifically, CD34+ cells failed to expand in vitro, B-cell development was compromised, and T-cells did not proliferate in long-term culture. Finally, we report on the natural history and outcome of our patients. While two patients died from infections, hematopoietic stem cell transplantation (HSCT resulted in sustained engraftment in two patients

Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

Science.gov (United States)

Speckmann, Carsten; Sahoo, Sushree Sangita; Rizzi, Marta; Hirabayashi, Shinsuke; Karow, Axel; Serwas, Nina Kathrin; Hoemberg, Marc; Damatova, Natalja; Schindler, Detlev; Vannier, Jean-Baptiste; Boulton, Simon J; Pannicke, Ulrich; Göhring, Gudrun; Thomay, Kathrin; Verdu-Amoros, J J; Hauch, Holger; Woessmann, Wilhelm; Escherich, Gabriele; Laack, Eckart; Rindle, Liliana; Seidl, Maximilian; Rensing-Ehl, Anne; Lausch, Ekkehart; Jandrasits, Christine; Strahm, Brigitte; Schwarz, Klaus; Ehl, Stephan R; Niemeyer, Charlotte; Boztug, Kaan; Wlodarski, Marcin W

2017-01-01

Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys, p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel heterozygous mutation p.Val796AlafsX4. The most unifying features were hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition, three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous recombination defect was detected in patient-derived fibroblasts but not in hematopoietic compartment. Notably, in both cellular compartments, differential expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts, response to ionizing irradiation and non-homologous end joining were not impaired. Telomeric circles did not accumulate in patient-derived primary cells and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative exhaustion, spontaneous apoptosis and senescence. Specifically, CD34 + cells failed to expand in vitro , B-cell development was compromised, and T-cells did not proliferate in long-term culture. Finally, we report on the natural history and outcome of our patients. While two patients died from infections, hematopoietic stem cell transplantation (HSCT) resulted in sustained engraftment in two patients. Whether

L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.

Science.gov (United States)

Choe, Chi-un; Nabuurs, Christine; Stockebrand, Malte C; Neu, Axel; Nunes, Patricia; Morellini, Fabio; Sauter, Kathrin; Schillemeit, Stefan; Hermans-Borgmeyer, Irm; Marescau, Bart; Heerschap, Arend; Isbrandt, Dirk

2013-01-01

Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus.

Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide

International Nuclear Information System (INIS)

Jakab, G.J.

1987-01-01

The effect of acute exposures to NO 2 on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. With S. aureus pulmonary antibacterial defenses were suppressed at NO 2 levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO 2 exposure prior to bacterial challenge) raised the threshold concentration for NO 2 -induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO 2 did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with 32 P-labeled staphylococci

ECG-triggered MDR-CT for the detection of pulmonary metastases

International Nuclear Information System (INIS)

Pauls, S.; Wahl, J.; Aschoff, A.J.; Brambs, H.J.; Fleiter, T.R.

2003-01-01

Purpose: Comparison of multidetector-row CT (MDR-CT) of the chest with and without ECG triggering for the detection of pulmonary metastases. Materials and Methods: Fifty patients with malignant tumors underwent CT of the chest. The unenhanced phase was performed with ECG-triggered MDR-CT and the contrast-enhanced phase with helical MDR-CT. The ECG-triggered and standard helical scans were interpreted in separate sessions, with the analysis determining the number and demarcation of the intrapulmonary nodules and the delineation of the mediastinal structure (rated 1 = excellent to 5 = poor). Results: ECG-MDR-CT images detected 38% more pulmonary nodules than MDR-CT. The detection rate for tumors [de

Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency.

Science.gov (United States)

Lopez-Gomez, Carlos; Levy, Rebecca J; Sanchez-Quintero, Maria J; Juanola-Falgarona, Martí; Barca, Emanuele; Garcia-Diaz, Beatriz; Tadesse, Saba; Garone, Caterina; Hirano, Michio

2017-05-01

Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2 -/- ) mice by 2- to 3-fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy. To test these hypotheses, we assessed two therapies in Tk2 -/- mice: (1) dT+dC and (2) coadministration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP. We observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2 -/- animals compared to dCMP+dTMP. Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652. © 2017 American Neurological Association.

Clinical manifestations of pulmonary and extra-pulmonary tuberculosis

African Journals Online (AJOL)

85% of reported tuberculosis cases were pulmonary ... Both pulmonary and nonpulmonary 32% ... 10% of patients with apparently localized tuberculosis ... mycetoma) in a cavity or erosion into an airway ... Dyspnoea is unusual unless there is extensive disease and ... via the airways into other parts of the lungs, causing a.

Analysis of human error and organizational deficiency in events considering risk significance

International Nuclear Information System (INIS)

Lee, Yong Suk; Kim, Yoonik; Kim, Say Hyung; Kim, Chansoo; Chung, Chang Hyun; Jung, Won Dea

2004-01-01

In this study, we analyzed human and organizational deficiencies in the trip events of Korean nuclear power plants. K-HPES items were used in human error analysis, and the organizational factors by Jacobs and Haber were used for organizational deficiency analysis. We proposed the use of CCDP as a risk measure to consider risk information in prioritizing K-HPES items and organizational factors. Until now, the risk significance of events has not been considered in human error and organizational deficiency analysis. Considering the risk significance of events in the process of analysis is necessary for effective enhancement of nuclear power plant safety by focusing on causes of human error and organizational deficiencies that are associated with significant risk

Iron-Deficiency Anemia

Science.gov (United States)

... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Clinical evaluation of pulmonary perfusion MRI using FAIR (flow-sensitive alternating inversion recovery)-HASTE (Half-Fourier Single-Shot TurboSE) method

International Nuclear Information System (INIS)

Togami, Izumi; Sasai, Nobuya; Tsunoda, Masatoshi; Sei, Tetsurou; Sato, Shuhei; Yabuki, Takayuki; Hiraki, Yoshio

2002-01-01

The FAIR-HASTE method is a kind of noninvasive perfusion MR imaging obtained without the use of contrast media. By subtracting a flow-insensitive image from a flow-sensitive image, contrast enhancement of inflowing blood achieved. In the present study, we applied pulmonary perfusion FAIR-HASTE sequence for 23 patients with various pulmonary diseases, and compared the findings with those by pulmonary perfusion scintigraphy and Gadolinium perfusion MRI. Pulmonary perfusion imaging with the FAIR-HASTE method was possible in all clinical cases, and the findings corresponded well to those obtained by perfusion MRI using contrast media or pulmonary scintigraphy. The FAIR-HASTE method is a promising method for the evaluation of pulmonary perfusion. (author)

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.

Directory of Open Access Journals (Sweden)

Simon Blankley

Full Text Available Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB.The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease.The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics.

HIV and Pulmonary Hypertension

Science.gov (United States)

... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

Does computer-assisted detection of pulmonary emboli enhance severity assessment and risk stratification in acute pulmonary embolism?

International Nuclear Information System (INIS)

Engelke, C.; Schmidt, S.; Auer, F.; Rummeny, E.J.; Marten, K.

2010-01-01

Aim: To prospectively assess the value of computer-aided detection (CAD) for the computed tomography (CT) severity assessment of acute pulmonary embolism (PE). Materials and methods: CT angiographic scans of 58 PE-positive patients (34-89 years, mean 66 years) were analysed by four observers for PE severity using the Mastora index, and by CAD. Patients were stratified to three PE risk groups and results compared to an independent reference standard. Interobserver agreement was tested by Bland and Altman and extended kappa (Ke) statistics. Mastora index changes after CAD data review were tested by Wilcoxon signed ranks. Results: CAD detected 343 out of 1118 emboli within given arterial segments and a total of 155 out of 218 polysegmental emboli (segmental vessel-based sensitivity = 30.7%, embolus-based sensitivity = 71.2% false-positive rate = 4.1/scan). Interobserver agreement on PE severity [95% limits of agreement (LOA) = -19.7-7.5% and-5.5-3% for reader pairs 1 versus 2 and 3 versus 4, respectively was enhanced by consensus with CAD data (LOA = -6.5-5.4% and-3.7-2% for reader pairs 1 versus 2 and 3 versus 4, respectively). Simultaneously, the percentual scoring errors (PSE) were significantly decreased (PSE = 35.4 ± 31.8% and 5.1 ± 8.9% for readers1/2 and 2/3, respectively, and PSE = 27.6 ± 31% and 3.8 ± 6.2%, respectively, after CAD consensus; p ≤ 0.005). Misclassifications to PE risk groups occurred in 27.6, 24.1, 5.2, and 5.2% of patients for readers 1-4, respectively, (Ke = 0.74) and were corrected by CAD consensus in 56.3, 36, 33.3, and 33.3% of misclassified patients, respectively (Ke = 0.83; p < 0.05). Conclusion: Radiologists may benefit from consensus with CAD data that improve PE severity scores and stratification to PE risk groups.

Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature.

Science.gov (United States)

Shifrin, Yulia; Sadeghi, Sina; Pan, Jingyi; Jain, Amish; Fajardo, Andres F; McNamara, Patrick J; Belik, Jaques

2015-11-15

The factors accounting for the pathological maintenance of a high pulmonary vascular (PV) resistance postnatally remain elusive, but neonatal stressors may play a role in this process. Cross-fostering in the immediate neonatal period is associated with adult-onset vascular and behavioral changes, likely triggered by early-in-life stressors. In hypothesizing that fostering newborn rats induces long-lasting PV changes, we evaluated them at 14 days of age during adulthood and compared the findings with animals raised by their biological mothers. Fostering resulted in reduced maternal-pup contact time when compared with control newborns. At 2 wk of age, fostered rats exhibited reduced pulmonary arterial endothelium-dependent relaxation secondary to downregulation of tissue endothelial nitric oxide synthase expression and tetrahydrobiopterin deficiency-induced uncoupling. These changes were associated with neonatal onset-increased ANG II receptor type 1 expression, PV remodeling, and right ventricular hypertrophy that persisted into adulthood. The pulmonary arteries of adult-fostered rats exhibited a higher contraction dose response to ANG II and thromboxane A2, the latter of which was abrogated by the oxidant scavenger Tempol. In conclusion, fostering-induced neonatal stress induces long-standing PV changes modulated via the renin-angiotensin system. Copyright © 2015 the American Physiological Society.

The impacts of phosphorus deficiency on the photosynthetic electron transport chain

DEFF Research Database (Denmark)

Carstensen, Andreas; Herdean, Andrei; Schmidt, Sidsel Birkelund

2018-01-01

light conditions. Under P deficiency, the enhanced electron flow through PSI increases the levels of NADPH, whereas ATP production remains restricted and hence reduces CO2 fixation. In parallel, lumen acidification activates the qE component of the non-photochemical quenching (NPQ) mechanism......Phosphorus (P) is an essential macronutrient, and P deficiency limits plant productivity. Recent work showed that P deficiency affects electron transport to photosystem I (PSI), but the underlying mechanisms are unknown. Here, we present a comprehensive biological model describing how P deficiency...... accumulate in the thylakoids and cause lumen acidification, which inhibits linear electron flow. Limited plastoquinol (PQH2) oxidation retards electron transport to the cytochrome (Cyt) b6f complex, yet the electron transfer rate of PSI is increased under steady-state growth light and is limited under high...

Dry eye in vitamin D deficiency: more than an incidental association.

Science.gov (United States)

Yildirim, Pelin; Garip, Yeşim; Karci, Ayse Aslihan; Guler, Tuba

2016-01-01

The aim of this article is two-fold: (i) to demonstrate the relation between vitamin D deficiency and dry eye and impaired tear function; and (ii) to investigate the possible associations among clinical parameters of hypovitaminosis D with dry eye parameters. Fifty premenopausal women with vitamin D deficiency (serum vitamin D levels dry eye parameters (P > 0.05). Vitamin D level was negatively correlated with OSDI (r = -0.49; P Dry eye and impaired tear function in patients with vitamin D deficiency may indicate a protective role of vitamin D in the development of dry eye, probably by enhancing tear film parameters and reducing ocular surface inflammation. Patients with vitamin D deficiency should be evaluated for dry eye syndromes. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis.

Directory of Open Access Journals (Sweden)

Karen L Wozniak

2009-09-01

Full Text Available Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-gamma-producing C. neoformans strain, H99gamma, results in complete protection against a second pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against pulmonary cryptococcosis in mice immunized with C. neoformans strain H99gamma compared to mice immunized with heat-killed C. neoformans (HKC.n.. Mice immunized with C. neoformans strain H99gamma had significantly reduced pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against pulmonary cryptococcosis was associated with increased pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of pulmonary inflammation, which protected the lungs from severe allergic bronchopulmonary mycosis (ABPM-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL-4 receptor, IL-12p40, IL-12p35, IFN-gamma, T cell and B cell deficient mice with C. neoformans strain H99gamma demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99gamma-mediated protective immune responses against pulmonary C. neoformans infection. CD4(+ T cells, CD11c(+ cells, and Gr-1(+ cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-gamma or TNF-alpha in lungs of protected mice. In conclusion, immunization with C

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

Directory of Open Access Journals (Sweden)

Cristian R. Astorga

2018-03-01

Full Text Available Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN, a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs.Methods: Twelve lambs (Ovis aries gestated and born at highlands (3,600 m were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1 during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations.Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05. This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05 and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05. Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05. Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05.Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

Science.gov (United States)

Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

An application of semiquantitative analysis of pulmonary scintigraphy to pulmonary tuberculosis sequelae

International Nuclear Information System (INIS)

Uchida, Kou; Miyasaka, Takashi; Nakayama, Hiroyuki; Suganuma, Yasuaki; Sim, Jae-Joon; Takahashi, Hideki; Takano, Masaaki; Kawata, Kanemitsu.

1996-01-01

We performed ventilation-perfusion scintigraphy in 13 patients with pulmonary tuberculosis sequelae and 21 with chronic obstructive pulmonary disease. We used 99m Tc-MAA for perfusion scintigram and 133 Xe gas for ventilation scintigram. We added the radioactivities during the rebreathing phase of the ventilation scintigram to make a computerized image of the lung volume. Regions of interest (ROIs) were derived from radioactivities on each image. ROIs included each whole lung on lung volume (L) image and areas where radioactivity was greater than 70% of the highest radioactivity on perfusion (P70) image. We counted the area of ROIs on L and P70, and used the ratio of perfusion to lung volume (P70/L) as a parameter of pulmonary perfusion. P70/L in patients with pulmonary tuberculosis sequelae was significantly higher than that in those with COPD. This suggested that the area of high pulmonary perfusion is larger in the patients with pulmonary tuberculosis sequelae as compared with those with COPD. (author)

Cystic pulmonary hydatidosis

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Malay Sarkar

2016-01-01

Full Text Available Cystic echinococcosis (CE is a zoonotic parasitic disease caused by the larval stages of the cestode Echinococcus granulosus. Worldwide, pulmonary hydatid cyst is a significant problem medically, socially, and economically. Surgery is the definitive therapy of pulmonary hydatidosis. Benzimidazoles may be considered in patients with a surgical contraindication. This review will focus on pathogenesis, lifecycle, clinical features, and management of pulmonary hydatid disease.

Isolated unilateral pulmonary artery hypoplasia with accompanying pulmonary parenchymal findings on CT: A case report

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Park, Surin; Cha, Yoon Ki; Kim, Jeung Sook; Kwon, Jae Hyun; Jeong, Yun Jeong [Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang (Korea, Republic of); Kim, Seon Jeong [Dept. of Radiology, Myongji Hospital, Goyang (Korea, Republic of)

2017-05-15

Unilateral pulmonary artery hypoplasia or agenesis without congenital cardiovascular anomalies is rare in adults. We report a case of a 36-year-old man with isolated left unilateral pulmonary artery hypoplasia with recurrent hemoptysis. On computed tomography (CT), the left pulmonary artery showed hypoplasia with multiple collateral vessels seen in the mediastinum and the left hemithorax. Also, parenchymal bands and peripheral linear opacities were seen in the affected lung, which were probably due to chronic infarction induced by unilateral pulmonary artery hypoplasia. There are only a few reports focusing on the radiologic findings in the pulmonary parenchyma induced by unilateral pulmonary artery hypoplasia, such as parenchymal bands and peripheral linear opacities. Therefore we report this case, which focused on the CT findings in the pulmonary parenchyma due to isolated unilateral pulmonary artery hypoplasia.

Isolated unilateral pulmonary artery hypoplasia with accompanying pulmonary parenchymal findings on CT: A case report

International Nuclear Information System (INIS)

Park, Surin; Cha, Yoon Ki; Kim, Jeung Sook; Kwon, Jae Hyun; Jeong, Yun Jeong; Kim, Seon Jeong

2017-01-01

Unilateral pulmonary artery hypoplasia or agenesis without congenital cardiovascular anomalies is rare in adults. We report a case of a 36-year-old man with isolated left unilateral pulmonary artery hypoplasia with recurrent hemoptysis. On computed tomography (CT), the left pulmonary artery showed hypoplasia with multiple collateral vessels seen in the mediastinum and the left hemithorax. Also, parenchymal bands and peripheral linear opacities were seen in the affected lung, which were probably due to chronic infarction induced by unilateral pulmonary artery hypoplasia. There are only a few reports focusing on the radiologic findings in the pulmonary parenchyma induced by unilateral pulmonary artery hypoplasia, such as parenchymal bands and peripheral linear opacities. Therefore we report this case, which focused on the CT findings in the pulmonary parenchyma due to isolated unilateral pulmonary artery hypoplasia

Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

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Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

2017-05-31

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

Scintigraphic study of blood perfusion of the pulmonary artery in pulmonary tuberculosis

International Nuclear Information System (INIS)

Certain, D.A.; Brolio, R.; Salomon, G.C.; Carvalho, N.; Barbosa, Z.L.M.

1972-01-01

Blood perfusion in the pulmonary artery is studied by pulmonary scintigraphy with macroaggregated albumin 131 I, in 74 cases of pulmonary tuberculosis. Results shown by scintigraphy are compared to those observed in roentgenography and also correlated with the extension and degree of the lesions, and with the presence of associated tuberculosis, considered capable of changing the scintigraphic picture. The reduction of blood flow in the pulmonary artery are observed in cases of infiltrative, fibrotic of caseous lesions, as well as in cases of minor lesions [pt

Scintigraphic study of blood perfusion of the pulmonary artery in pulmonary tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Certain, D A; Brolio, R; Salomon, G C [Sao Paulo Univ. (Brazil). Faculdade de Saude Publica; Carvalho, N [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear; Barbosa, Z L.M. [Associacao dos Sanatorios Populares de Campos do Jordao, Brazil

1972-10-01

Blood perfusion in the pulmonary artery is studied by pulmonary scintigraphy with macroaggregated albumin /sup 131/I, in 74 cases of pulmonary tuberculosis. Results shown by scintigraphy are compared to those observed in roentgenography and also correlated with the extension and degree of the lesions, and with the presence of associated tuberculosis, considered capable of changing the scintigraphic picture. The reduction of blood flow in the pulmonary artery are observed in cases of infiltrative, fibrotic of caseous lesions, as well as in cases of minor lesions.

Pulmonary Hypertension in Scleroderma

Science.gov (United States)

PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels of the lungs. If the high ... the right side of the heart. Patients with scleroderma are at increased risk for developing PH from ...

Pulmonary manifestations of malaria

International Nuclear Information System (INIS)

Rauber, K.; Enkerlin, H.L.; Riemann, H.; Schoeppe, W.; Frankfurt Univ.

1987-01-01

We report on the two different types of pulmonary manifestations in acute plasmodium falciparum malaria. The more severe variant shows long standing interstitial pulmonary infiltrates, whereas in the more benign courses only short-term pulmonary edemas are visible. (orig.) [de

Nonviral pulmonary delivery of siRNA.

Science.gov (United States)

Merkel, Olivia M; Kissel, Thomas

2012-07-17

target site. In addition, the ideal carrier would be biodegradable (to address difficulties with repeated administration for the treatment of chronic diseases) and would contain targeting moieties to enhance uptake by specific cell types. None of the currently available polymer- and lipid-based formulations meet every one of these requirements, but we introduce here several promising new approaches, including a biodegradable, nonimmunogenic polyester. We also discuss imaging techniques for following the biodistribution according to the administration route. This tracking is crucial for better understanding the translocation and clearance of nanoformulated siRNA subsequent to pulmonary delivery. In the literature, the success of pulmonary siRNA delivery is evaluated solely by relief from or prophylaxis against a disease; side effects are not studied in detail. It also remains unclear which cell types in the lung eventually take up siRNA. These are critical issues for the translational use of pulmonary siRNA formulations; accordingly, we present a flow cytometry technique that can be utilized to differentiate transfected cell populations in a mouse model that expresses transgenic enhanced green fluorescence protein (EGFP). This technique, in which different cell types are identified on the basis of their surface antigen expression, may eventually help in the development of safer carriers with minimized side effects in nontargeted tissues.

Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

Science.gov (United States)

Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt

2017-06-01

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts. © 2017 Wiley Periodicals, Inc.

Pulmonary venous varix associated with mitral regurgitation mimicking a mediastinal mass: A case report and review of the literature

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Dana AlNuaimi, MD

2018-04-01

Full Text Available Pulmonary vein varix is an unusual cause of a mediastinal mass on a chest radiograph. It may be found as an isolated malformation or as a sequela of pulmonary venous hypertension. We encountered a case presenting with left hemiparesis and a past medical history of rheumatic heart disease. The chest radiograph revealed a well-defined mediastinal mass that turned out to be a hugely dilated pulmonary vein on contrast enhanced computed tomography of the chest. The computed tomography of the brain and upper abdomen revealed bilateral cerebral infarction and splenic infarction. In the literature, one-third of the reported cases of pulmonary vein varix are acquired secondary to mitral valve disease. Keywords: Pulmonary venous varix, Mitral valve insufficiency, Cerebral infarction, Splenic infarction, Computed tomography