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Sample records for impaired lung function

  1. Metabolic Syndrome Biomarkers Predict Lung Function Impairment

    PubMed Central

    Naveed, Bushra; Weiden, Michael D.; Kwon, Sophia; Gracely, Edward J.; Comfort, Ashley L.; Ferrier, Natalia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

    2012-01-01

    Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre–September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing

  2. Particulate air pollution and impaired lung function

    PubMed Central

    Paulin, Laura; Hansel, Nadia

    2016-01-01

    Air pollution is a leading cause of morbidity and mortality throughout the world, particularly in individuals with existing lung disease. Of the most common air pollutants, particulate matter (PM) is associated with an increased risk of exacerbations and respiratory symptoms in individuals with existing lung disease, and to a lesser extent, in those without known respiratory issues. The majority of published research has focused on the effects of PM exposures on symptoms and health care utilization. Fewer studies focus on the impact of PM on objective measurements of pulmonary function. This review will focus on the effects of PM exposure on objective measurements of lung function in both healthy individuals and those with existing lung disease. PMID:26962445

  3. Particulate air pollution and impaired lung function.

    PubMed

    Paulin, Laura; Hansel, Nadia

    2016-01-01

    Air pollution is a leading cause of morbidity and mortality throughout the world, particularly in individuals with existing lung disease. Of the most common air pollutants, particulate matter (PM) is associated with an increased risk of exacerbations and respiratory symptoms in individuals with existing lung disease, and to a lesser extent, in those without known respiratory issues. The majority of published research has focused on the effects of PM exposures on symptoms and health care utilization. Fewer studies focus on the impact of PM on objective measurements of pulmonary function. This review will focus on the effects of PM exposure on objective measurements of lung function in both healthy individuals and those with existing lung disease. PMID:26962445

  4. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  5. Characterization of Lung Function Impairment in Adults with Bronchiectasis

    PubMed Central

    Lin, Zhi-ya; Tang, Yan; Li, Hui-min; Lin, Zhi-min; Zheng, Jin-ping; Chen, Rong-chang; Zhong, Nan-shan

    2014-01-01

    Background Characteristics of lung function impairment in bronchiectasis is not fully understood. Objectives To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). Methods We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. Results In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Conclusion Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. Trial Registration ClinicalTrials.gov NCT01761214 PMID:25405614

  6. [Impaired lung function in patients with moderate chronic obstructive bronchitis].

    PubMed

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

    2004-01-01

    VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex, DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were found to have impaired bronchial patency, 90.9% of the patients had lung volume and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%. Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC. Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a reduction and an increase in paCO2. The magnitude of the functional changes observed in most patients was low. Significant and pronounced disorders were seen in one third of the patients. PMID:15719666

  7. Proteasome function is not impaired in healthy aging of the lung.

    PubMed

    Caniard, Anne; Ballweg, Korbinian; Lukas, Christina; Yildirim, Ali Ö; Eickelberg, Oliver; Meiners, Silke

    2015-10-01

    Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging. PMID:26540298

  8. Proteasome function is not impaired in healthy aging of the lung

    PubMed Central

    Lukas, Christina; Yildirim, Ali Ö.; Eickelberg, Oliver; Meiners, Silke

    2015-01-01

    Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age‐related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase‐like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging. PMID:26540298

  9. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  10. Older Adults with Chronic Lung Disease Report Less Limitation Compared with Younger Adults with Similar Lung Function Impairment

    PubMed Central

    Han, Meilan K.; Thompson, Bruce; Limper, Andrew H.; Martinez, Fernando J.; Schwarz, Marvin I.; Sciurba, Frank C.; Criner, Gerald J.; Wise, Robert A.

    2015-01-01

    Rationale: Disability guidelines are often based on pulmonary function testing, but factors other than lung function influence how an individual experiences physiologic impairment. Age may impact the perception of impairment in adults with chronic lung disease. Objectives: To determine if self-report of physical functional impairment differs between older adults with chronic lung disease compared with younger adults with similar degrees of lung function impairment. Methods: The Lung Tissue Research Consortium provided data on 981 participants with chronic obstructive pulmonary disease and interstitial lung disease who were well characterized with clinical, radiological, and pathological diagnoses. We used multiple logistic regression to determine if responses to health status questions (from the Short Form-12 and St. George’s Respiratory Questionnaire) related to perception of impairment differed in older adults (age ≥ 65 yr, n = 427) compared with younger adults (age < 65 yr, n = 393). Measurements and Main Results: Pulmonary function was higher in older adults (median FEV1 %, 70) compared with younger adults (median FEV1 %, 62) (P < 0.001), whereas the median 6-minute-walk distance was similar between groups (372 m vs. 388 m, P = 0.21). After adjusting for potential confounders, older adults were less likely to report that their health limited them significantly in performing moderate activities (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.22–0.58) or climbing several flights of stairs (OR, 0.51; 95% CI, 0.34–0.77). The odds of reporting that their physical health limited the kinds of activities they performed were reduced by 63% in older adults (OR, 0.37; 95% CI, 0.24–0.58), and, similarly, the odds of reporting that their health caused them to accomplish less than they would like were also lower in older adults (OR, 0.39; 95% CI, 0.25–0.60). The OR for reporting that their breathing problem stops them from doing most

  11. Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

    PubMed

    Li, Guanggang; Cao, Yinghua; Sun, Yue; Xu, Ruxiang; Zheng, Zhendong; Song, Haihan

    2016-09-01

    Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs. PMID:27179778

  12. Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

    PubMed

    Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

    2016-07-01

    Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. PMID:27136672

  13. Bronchoalveolar lavage cell analysis and lung function impairment in patients with systemic lupus erythematosus (SLE).

    PubMed Central

    Groen, H; Aslander, M; Bootsma, H; van der Mark, T W; Kallenberg, C G; Postma, D S

    1993-01-01

    We examined the relationship between peripheral blood and bronchoalveolar lavage (BAL) lymphocyte phenotypes and lung function in 19 patients with SLE, and evaluated their association with disease activity. Lung function assessment showed a mildly restrictive pattern with frequent impairment of transfer factor for carbon monoxide (T1,co) and diffusing capacity of the alveolocapillary membrane (Dm), of late-expiratory airflow rates and with a high prevalence of increased airway resistance. T1,co, Kco and Dm correlated inversely with the numbers of CD8+ cells and CD56+/CD16+/CD3- (NK) cells in BAL. Oxygen radical production, both by stimulated and unstimulated BAL cells and blood polymorphonuclear leucocytes (PMN) was significantly increased in SLE. In comparison with healthy controls, patients with SLE had a lower percentage of CD19+ B cells in the BAL versus an increased percentage of these cells in peripheral blood. HLA-DR expression on CD4+ and CD8+ lung lymphocytes was markedly increased in SLE. Current SLE disease activity was not associated with changes in BAL or peripheral blood lymphocyte phenotypes. Our data suggest that an ongoing cell-mediated immune response is present in the lungs in SLE, particularly involving activated CD8+ T cells and CD56+/CD16+/CD3- NK cells. It is associated with up-regulated local production of oxygen radicals and with impaired pulmonary diffusing capacity. This inflammatory process seems to be independent of general SLE disease activity. PMID:8403494

  14. Relationship Between Lung Function Impairment and Health-Related Quality of Life in COPD and Interstitial Lung Disease

    PubMed Central

    Berry, Cristine E.; Drummond, M. Bradley; Han, MeiLan K.; Li, Daner; Fuller, Cathy; Limper, Andrew H.; Martinez, Fernando J.; Schwarz, Marvin I.; Sciurba, Frank C.

    2012-01-01

    Background: Health-related quality-of-life (HRQL) measures have been correlated with lung function in patients with COPD and interstitial lung disease (ILD). However, different pathophysiologic mechanisms may influence how these distinct diseases affect HRQL, resulting in differing HRQL by pulmonary diagnosis among patients with similar severity of ventilatory impairment. Methods: The National Heart, Lung, and Blood Institute Lung Tissue Research Consortium provided data on well-characterized participants with COPD (n = 576) and ILD (n = 405) at four clinical sites. Using multiple linear regression, we examined the effects of FEV1 (% predicted) and diagnosis (ILD vs COPD) on HRQL scores, including total St. George Respiratory Questionnaire (SGRQ) scores and Short Form-12 (SF-12) physical component summary (PCS) and mental component summary (MCS) scores. Results: Participants with ILD had, on average, higher SGRQ scores (15.33 points; 95% CI, 12.46-18.19; P <.001) and lower SF-12 PCS scores ( − 4.73 points; 95% CI, − 6.31 to − 3.14; P <.001) compared with patients with COPD with similar FEV1 % predicted values, indicating worse HRQL. The specific diagnosis also modified the effect of FEV1 on the total SGRQ score (P = .003) and the SF-12 PCS score (P = .03). There was no relationship between lung function and SF-12 MCS scores. Conclusions: HRQL scores were worse for patients with ILD compared with patients with COPD with similar degrees of ventilatory impairment. Differences in dyspnea mechanism or in the rate of disease progression may account for these differences in HRQL. PMID:22576634

  15. Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients

    PubMed Central

    Mazzuco, Adriana; Medeiros, Wladimir Musetti; Sperling, Milena Pelosi Rizk; de Souza, Aline Soares; Alencar, Maria Clara Noman; Arbex, Flávio Ferlin; Neder, José Alberto; Arena, Ross; Borghi-Silva, Audrey

    2015-01-01

    Background In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses. We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD. Methods Sixteen sedentary males with COPD were enrolled in this study. Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured. The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA). Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated. Results HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio. Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=−0.53 (P<0.05). Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=−0.77, r2=0.43, P<0.05). Conclusion Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients. PMID:26316739

  16. Gender differences in the effect of occupational endotoxin exposure on impaired lung function and death: the Shanghai Textile Worker Study

    PubMed Central

    Zhang, Feng-ying; Lin, Xinyi; Zheng, Bu-yong; Dai, Hei-Lian; Su, Li; Cai, Tianxi; Christiani, David C.

    2014-01-01

    OBJECTIVE Airborne endotoxin exposure has both adverse and protective health effects. Studies show males have augmented acute inflammatory responses to endotoxin. In this longitudinal cohort study we investigated the effect of long-term exposure to endotoxin in cotton dust on health, and determined whether these effects differ by gender. METHODS In the Shanghai Textile Worker Study, 447 cotton and 472 control silk textile workers were followed from 1981 to 2011 with repeated measures of occupational endotoxin exposure, spirometry, and health questionnaires. Impaired lung function was defined as a decline in forced expiratory volume in one second to less than the 5th percentile of population predicted. Death was ascertained by death registries. We used Cox proportional hazards models to assess the effect of endotoxin exposure on the time to development of impaired lung function and death. RESULTS 128 deaths and 164 diagnoses of impaired lung function were ascertained between 1981 and 2011. Hazard ratios (HRs) for the composite endpoint of impaired lung function or death was 1.47 (95% CI 1.09-1.97) for cotton vs. silk workers and 1.04 (95% CI 1.01-1.07) per 10,000 endotoxin units (EU)/m3-years increase in exposure. HRs for all-cause mortality was 1.36 (95% CI 0.93-1.99) for cotton vs. silk workers and 1.04 (95% CI 0.99-1.08) per 10,000 EU/m3-years. The risk associated with occupational endotoxin exposure was elevated only in men. CONCLUSIONS Occupational endotoxin exposure is associated with an increase in the risk of impaired lung function and all-cause mortality in men. PMID:24297825

  17. Chest imaging and lung function impairment after long-term occupational exposure to low concentrations of chrysotile.

    PubMed

    Spyratos, Dionisios; Chloros, Diamantis; Haidich, Bettina; Dagdilelis, Loukas; Markou, Stamatia; Sichletidis, Lazaros

    2012-01-01

    The aim of the present study was the investigation of radiographic findings in relation to lung function after occupational exposure to permissible levels of relatively pure chrysotile (0.5-3% amphiboles). We studied 266 out of the total 317 employees who have worked in an asbestos cement factory during the period 1968-2004 with chest x-ray, high-resolution computed tomography (HRCT) and lung function tests. Sensitivity of chest x-ray was 43% compared to HRCT. Abnormal HRCT findings were found in 75 subjects (67%) and were related to age, occupational exposure duration, and spirometric data. The presence of parenchymal or visceral pleural lesions (exclusively or as the predominant abnormality) was being accompanied by lower total lung capacity and diffusion capacity. HRCT was much more sensitive than chest x-ray for occupational chrysotile exposure. Lung function impairment was related with parenchymal but not with pleural HRCT abnormalities. PMID:22524648

  18. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

    PubMed Central

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T.; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. PMID:26068229

  19. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T; Kallen, Caleb B; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. PMID:26068229

  20. Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2/EP2 signaling

    PubMed Central

    Medeiros, Alexandra I.; Serezani, Carlos H.; Lee, Sang Pyo; Peters-Golden, Marc

    2009-01-01

    The ingestion of apoptotic cells (ACs; termed “efferocytosis”) by phagocytes has been shown to trigger the release of molecules such as transforming growth factor β, interleukin-10 (IL-10), nitric oxide, and prostaglandin E2 (PGE2). Although the antiinflammatory actions of these mediators may contribute to the restoration of homeostasis after tissue injury, their potential impact on antibacterial defense is unknown. The lung is highly susceptible to diverse forms of injury, and secondary bacterial infections after injury are of enormous clinical importance. We show that ACs suppress in vitro phagocytosis and bacterial killing by alveolar macrophages and that this is mediated by a cyclooxygenase–PGE2–E prostanoid receptor 2 (EP2)–adenylyl cyclase–cyclic AMP pathway. Moreover, intrapulmonary administration of ACs demonstrated that PGE2 generated during efferocytosis and acting via EP2 accounts for subsequent impairment of lung recruitment of polymorphonuclear leukocytes and clearance of Streptococcus pneumoniae, as well as enhanced generation of IL-10 in vivo. These results suggest that in addition to their beneficial homeostatic influence, antiinflammatory programs activated by efferocytosis in the lung have the undesirable potential to dampen innate antimicrobial responses. They also identify an opportunity to reduce the incidence and severity of pneumonia in the setting of lung injury by pharmacologically targeting synthesis of PGE2 or ligation of EP2. PMID:19124657

  1. Lung CD8+ T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+ T Cells

    PubMed Central

    Wen, Sherry C.; Schuster, Jennifer E.; Gilchuk, Pavlo; Boyd, Kelli L.; Joyce, Sebastian

    2015-01-01

    ABSTRACT Human metapneumovirus (HMPV) is a major cause of respiratory disease in infants, the elderly, and immunocompromised individuals worldwide. There is currently no licensed HMPV vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate because they are noninfectious and elicit a neutralizing antibody response. However, studies show that serum neutralizing antibodies are insufficient for complete protection against reinfection and that adaptive T cell immunity is important for viral clearance. HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment, mediated by programmed death 1 (PD-1). In this study, we generated HMPV VLPs by expressing the fusion and matrix proteins in mammalian cells and tested whether VLP immunization induces functional HMPV-specific TCD8 responses in mice. C57BL/6 mice vaccinated twice with VLPs and subsequently challenged with HMPV were protected from lung viral replication for at least 20 weeks postimmunization. A single VLP dose elicited F- and M-specific lung TCD8s with higher function and lower expression of PD-1 and other inhibitory receptors than TCD8s from HMPV-infected mice. However, after HMPV challenge, lung TCD8s from VLP-vaccinated mice exhibited inhibitory receptor expression and functional impairment similar to those of mice experiencing secondary infection. HMPV challenge of VLP-immunized μMT mice also elicited a large percentage of impaired lung TCD8s, similar to mice experiencing secondary infection. Together, these results indicate that VLPs are a promising vaccine candidate but do not prevent lung TCD8 impairment upon HMPV challenge. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of acute respiratory disease for which there is no licensed vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate and induce antibodies, but T cell responses are less defined. Moreover, HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment mediated by

  2. Long-term ambient air pollution and lung function impairment in Chinese children from a high air pollution range area: The Seven Northeastern Cities (SNEC) study

    NASA Astrophysics Data System (ADS)

    Zeng, Xiao-Wen; Vivian, Elaina; Mohammed, Kahee A.; Jakhar, Shailja; Vaughn, Michael; Huang, Jin; Zelicoff, Alan; Xaverius, Pamela; Bai, Zhipeng; Lin, Shao; Hao, Yuan-Tao; Paul, Gunther; Morawska, Lidia; Wang, Si-Quan; Qian, Zhengmin; Dong, Guang-Hui

    2016-08-01

    Epidemiological studies have reported inconsistent and inconclusive associations between long-term exposure to ambient air pollution and lung function in children from Europe and America, where air pollution levels were typically low. The aim of the present study is to examine the relationship between air pollutants and lung function in children selected from heavily industrialized and polluted cities in northeastern China. During 2012, 6740 boys and girls aged 7-14 years were recruited in 24 districts of seven northeastern cities. Portable electronic spirometers were used to measure lung function. Four-year average concentrations of particulate matter with an aerodynamic diameter ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were measured at monitoring stations in the 24 districts. Two-staged regression models were used in the data analysis, controlling for covariates. Overall, for all subjects, the increased odds of lung function impairment associated with exposure to air pollutants, ranged from 5% (adjusted odds ratio [aOR] = 1.05; 95% confidence interval [CI] = 1.01, 1.10) for FVC < 85% predicted per 46.3 μg/m3 for O3 to 81% (aOR = 1.81; 95%CI = 1.44, 2.28) for FEV1 < 85% predicted per 30.6 μg/m3 for PM10. The linear regression models consistently showed a negative relationship between all air pollutants and lung function measures across subjects. There were significant interaction terms indicating gender differences for lung function impairment and pulmonary function from exposure to some pollutants (P < 0.10). In conclusion, long term exposure to high concentrations of ambient air pollution is associated with decreased pulmonary function and lung function impairment, and females appear to be more susceptible than males.

  3. Overweight and obesity as risk factors for impaired lung function in patients with asthma: A real-life experience.

    PubMed

    Ciprandi, Giorgio; Schiavetti, Irene; Bellezza Fontana, Rossana; Sorbello, Valentina; Ricciardolo, Fabio L M

    2014-01-01

    Several studies have outlined a possible relationship between an increased body mass index (BMI) and asthma. The aim of the study was to investigate in patients with asthma, enrolled in a real-life setting, a possible relationship between BMI and asthma parameters, including lung function markers (i.e., forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1/FVC ratio, and forced expiratory flow at 25-75%), fractional concentration of exhaled nitric oxide (FeNO), asthma control level, Asthma Control Test (ACT), comorbid allergy, and allergic rhinitis (AR). The study included 286 patients with asthma. All subjects were evaluated performing clinical examination, spirometry, FeNO measurement, and ACT questionnaire. Ninety-six (33.6%) patients were overweight and 45 (14.1%) patients were obese. Lung function was significantly impaired in overweight and obese asthmatic patients in comparison with normal-weight ones. Increased BMI did not affect FeNO values and asthma control level. Overweight patients had double the risk (odds ratio [OR], 1.89) and obese patients had triple the risk (OR, 3.17) of having pathological FEV1 in comparison with normal-weight patients. Both in overweight (OR, 2.415) and obese patients (OR, 2.126), the risk to have pathological FEV1/FVC was about two times higher than in normal-weight patients. In overweight and obese asthmatic patients the probability of allergy was, respectively, 3.5 times (OR, 0.285) and 4.5 times (OR, 0.224) lower compared with normal-weight asthmatic patients. The risk of suffering from AR was three times lower in overweight (OR, 0.331) patients and six times lower in obese (OR, 0.163) patients. The present study suggests that BMI assessment should be routinely considered in asthmatic patients to reveal bronchial obstruction, also, in controlled asthma. PMID:24992544

  4. Impaired function of CTLA-4 in the lungs of patients with chronic beryllium disease contributes to persistent inflammation.

    PubMed

    Chain, Jennifer L; Martin, Allison K; Mack, Douglas G; Maier, Lisa A; Palmer, Brent E; Fontenot, Andrew P

    2013-08-15

    Chronic beryllium disease (CBD) is an occupational lung disorder characterized by granulomatous inflammation and the accumulation of beryllium-responsive CD4(+) T cells in the lung. These differentiated effector memory T cells secrete IL-2, IFN-γ, and TNF-α upon in vitro activation. Beryllium-responsive CD4(+) T cells in the lung are CD28 independent and have increased expression of the coinhibitory receptor, programmed death 1, resulting in Ag-specific T cells that proliferate poorly yet retain the ability to express Th1-type cytokines. To further investigate the role of coinhibitory receptors in the beryllium-induced immune response, we examined the expression of CTLA-4 in blood and bronchoalveolar lavage cells from subjects with CBD. CTLA-4 expression was elevated on CD4(+) T cells from the lungs of study subjects compared with blood. Furthermore, CTLA-4 expression was greatest in the beryllium-responsive subset of CD4(+) T cells that retained the ability to proliferate and express IL-2. Functional assays show that the induction of CTLA-4 signaling in blood cells inhibited beryllium-induced T cell proliferation while having no effect on the proliferative capacity of beryllium-responsive CD4(+) T cells in the lung. Collectively, our findings suggest a dysfunctional CTLA-4 pathway in the lung and its potential contribution to the persistent inflammatory response that characterizes CBD. PMID:23851684

  5. Impaired mesenchymal cell function in Gata4 mutant mice leads to diaphragmatic hernias and primary lung defects

    PubMed Central

    Jay, Patrick Y.; Bielinska, Malgorzata; Erlich, Jonathan M.; Mannisto, Susanna; Pu, William T.; Heikinheimo, Markku; Wilson, David B.

    2007-01-01

    Congenital diaphragmatic hernia (CDH) is an often fatal birth defect that is commonly associated with pulmonary hypoplasia and cardiac malformations. Some investigators hypothesize that this constellation of defects results from genetic or environmental triggers that disrupt mesenchymal cell function in not only the primordial diaphragm but also the thoracic organs. The alternative hypothesis is that the displacement of the abdominal viscera in the chest secondarily perturbs the development of the heart and lungs. Recently, loss-of-function mutations in the gene encoding FOG-2, a transcriptional co-regulator, have been linked to CDH and pulmonary hypoplasia in humans and mice. Here we show that mutagenesis of the gene for GATA-4, a transcription factor known to functionally interact with FOG-2, predisposes inbred mice to a similar set of birth defects. Analysis of wild-type mouse embryos demonstrated co-expression of Gata4 and Fog2 in mesenchymal cells of the developing diaphragm, lungs, and heart. A significant fraction of C57Bl/6 mice heterozygous for a Gata4 deletion mutation died within one day of birth. Developmental defects in the heterozygotes included midline diaphragmatic hernias, dilated distal airways, and cardiac malformations. Heterozygotes had any combination of these defects or none. In chimeric mice, Gata4−/− cells retained the capacity to contribute to cells in the diaphragmatic central tendon and lung mesenchyme, indicating that GATA-4 is not required for differentiation of these lineages. We conclude that GATA-4, like its co-regulator FOG-2, is required for proper mesenchymal cell function in the developing diaphragm, lungs, and heart. PMID:17069789

  6. Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy

    PubMed Central

    Ravimohan, Shruthi; Tamuhla, Neo; Kung, Shiang-Ju; Nfanyana, Kebatshabile; Steenhoff, Andrew P.; Gross, Robert; Weissman, Drew; Bisson, Gregory P.

    2015-01-01

    Background HIV-infected patients with pulmonary TB (pTB) can have worsening of respiratory symptoms as part of TB-immune reconstitution inflammatory syndrome (TB-IRIS) following antiretroviral therapy (ART) initiation. Thus, reconstitution of immune function on ART could drive incident lung damage in HIV/TB. Methods We hypothesized that increases in matrix metalloproteinases (MMPs), which can degrade lung matrix, on ART are associated with TB-IRIS among a cohort of advanced, ART naïve, HIV-infected adults with pTB. Furthermore, we related early changes in immune measures and MMPs on ART to lung function in an exploratory subset of patients post-TB cure. This study was nested within a prospective cohort study. Rank sum and chi-square tests, Spearman's correlation coefficient, and logistic regression were used for analyses. Results Increases in MMP-8 following ART initiation were independently associated with TB-IRIS (p = 0.04; adjusted odds ratio 1.5 [95% confidence interval: 1.0–2.1]; n = 32). Increases in CD4 counts and MMP-8 on ART were also associated with reduced forced expiratory volume in one-second post-TB treatment completion (r = − 0.7, p = 0.006 and r = − 0.6, p = 0.02, respectively; n = 14). Conclusions ART-induced MMP increases are associated with TB-IRIS and may affect lung function post-TB cure. End-organ damage due to TB-IRIS and mechanisms whereby immune restoration impairs lung function in pTB deserve further investigation. PMID:27014741

  7. Impaired caveolae function and upregulation of alternative endocytic pathways induced by experimental modulation of intersectin-1s expression in mouse lung endothelium.

    PubMed

    Predescu, Dan N; Neamu, Radu; Bardita, Cristina; Wang, Minhua; Predescu, Sanda A

    2012-01-01

    Intersectin-1s (ITSN-1s), a protein containing five SH3 (A-E) domains, regulates via the SH3A the function of dynamin-2 (dyn2) at the endocytic site. ITSN-1s expression was modulated in mouse lung endothelium by liposome delivery of either a plasmid cDNA encoding myc-SH3A or a specific siRNA targeting ITSN-1 gene. The lung vasculature of SH3A-transduced and ITSN-1s- deficient mice was perfused with gold albumin (Au-BSA) to analyze by electron microscopy the morphological intermediates and pathways involved in transendothelial transport or with dinitrophenylated (DNP)-BSA to quantify by ELISA its transport. Acute modulation of ITSN-1s expression decreased the number of caveolae, impaired their transport, and opened the interendothelial junctions, while upregulating compensatory nonconventional endocytic/transcytotic structures. Chronic inhibition of ITSN-1s further increased the occurrence of nonconventional intermediates and partially restored the junctional integrity. These findings indicate that ITSN-1s expression is required for caveolae function and efficient transendothelial transport. Moreover, our results demonstrate that ECs are highly adapted to perform their transport function while maintaining lung homeostasis. PMID:22506115

  8. Impaired Caveolae Function and Upregulation of Alternative Endocytic Pathways Induced by Experimental Modulation of Intersectin-1s Expression in Mouse Lung Endothelium

    PubMed Central

    Predescu, Dan N.; Neamu, Radu; Bardita, Cristina; Wang, Minhua; Predescu, Sanda A.

    2012-01-01

    Intersectin-1s (ITSN-1s), a protein containing five SH3 (A-E) domains, regulates via the SH3A the function of dynamin-2 (dyn2) at the endocytic site. ITSN-1s expression was modulated in mouse lung endothelium by liposome delivery of either a plasmid cDNA encoding myc-SH3A or a specific siRNA targeting ITSN-1 gene. The lung vasculature of SH3A-transduced and ITSN-1s- deficient mice was perfused with gold albumin (Au-BSA) to analyze by electron microscopy the morphological intermediates and pathways involved in transendothelial transport or with dinitrophenylated (DNP)-BSA to quantify by ELISA its transport. Acute modulation of ITSN-1s expression decreased the number of caveolae, impaired their transport, and opened the interendothelial junctions, while upregulating compensatory nonconventional endocytic/transcytotic structures. Chronic inhibition of ITSN-1s further increased the occurrence of nonconventional intermediates and partially restored the junctional integrity. These findings indicate that ITSN-1s expression is required for caveolae function and efficient transendothelial transport. Moreover, our results demonstrate that ECs are highly adapted to perform their transport function while maintaining lung homeostasis. PMID:22506115

  9. Lung function and radiation response.

    PubMed

    Hong, A; Dische, S; Saunders, M I; Lockwood, P; Crocombe, K

    1991-12-01

    This study investigated whether impaired respiratory function affected the response to radiotherapy. A prospective study was performed in which lung function, arterial oxygen and haemoglobin concentration were examined, before treatment with radical radiotherapy, in 141 patients with advanced non-small cell lung cancer and head and neck cancer. The findings were considered to reflect the physiological conditions present at the time of radiotherapy and these were related to acute normal tissue reactions and tumour control. Although 53% of the patients showed some impairment of lung function and 47% demonstrated a haemoglobin oxygen saturation below the normal range, oxygen partial pressure was below expected levels in fewer patients (27%) and total arterial oxygen content was below normal in only 12% of patients. No correlation was found between the tests performed and the severity of acute morbidity or with local tumour control. In the patients with carcinoma of the bronchus, there was a trend for incomplete tumour control to be associated with a lower haemoglobin level, but this did not reach statistical significance. In patients selected for curative radiotherapy, lung function would not appear to be an important factor influencing the response of normal tissues or tumour to irradiation. PMID:1663411

  10. Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

    PubMed Central

    2011-01-01

    Background Is Impulse Oscillometry System (IOS) a valuable tool to measure respiratory system function in Children? Asthma (A) is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI) and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC) and augmented RIC (aRIC) models have emerged, which offer advantages over earlier models. Methods IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B) and post- bronchodilation (post-B) conditions over a period of 2 years. Results and Discussion Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H) and Small Airway-Impaired (SAI). The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children. The two model parameters: peripheral compliance (Cp) and peripheral resistance (Rp) tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle") showed good correlations. Conclusions What are the most useful IOS and model parameters? In this work we

  11. Dimethylfumarate Impairs Neutrophil Functions.

    PubMed

    Müller, Susen; Behnen, Martina; Bieber, Katja; Möller, Sonja; Hellberg, Lars; Witte, Mareike; Hänsel, Martin; Zillikens, Detlef; Solbach, Werner; Laskay, Tamás; Ludwig, Ralf J

    2016-01-01

    Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates-in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases. PMID:26763431

  12. CAVEOLINS AND LUNG FUNCTION

    PubMed Central

    Maniatis, Nikolaos A.; Chernaya, Olga; Shinin, Vasily; Minshall, Richard D.

    2012-01-01

    The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases. PMID:22411320

  13. Caveolins and lung function.

    PubMed

    Maniatis, Nikolaos A; Chernaya, Olga; Shinin, Vasily; Minshall, Richard D

    2012-01-01

    The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases. PMID:22411320

  14. T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

    PubMed Central

    Iriguchi, Shoichi; Kikuchi, Norihiro; Noguchi, Emiko; Morishima, Yuko; Matsuyama, Masashi; Yoh, Keigyou; Takahashi, Satoru; Nakauchi, Hiromitsu; Ishii, Yukio

    2015-01-01

    Although overexpression of T-bet, a master transcription factor in type-1 helper T lymphocytes, has been reported in several hematologic and immune diseases, its role in their pathogenesis is not fully understood. In the present study, we used transgenic model mice (T-bettg/wt and T-bettg/tg) to investigate the effects of T-bet overexpression selectively in T lymphocytes on the development of hematologic and immune diseases. The results showed that T-bet overexpression in T cells spontaneously induced maturation arrest in the mononuclear phagocyte lineage, as well as spontaneous dermatitis and pulmonary alveolar proteinosis (PAP)-like disease in T-bettg/wt and T-bettg/tg mice, respectively. T-bettg/tg alveoli with the PAP phenotype showed remarkable reorganization of alveolar mononuclear phagocyte subpopulations and impaired function, in addition to augmented T-cell infiltration. In addition, PAP development in T-bettg/tg mice was found to be associated with increased migration of myeloid cells from the bone marrow into the peripheral blood. These findings reveal an unexpected link between T-bet overexpression in T lymphocytes and the development of PAP caused by reorganization of mononuclear phagocytes in the lung, and provide new insight into the molecular pathogenesis of secondary PAP accompanied by hematologic disorders. PMID:25349175

  15. Minnelide/Triptolide Impairs Mitochondrial Function by Regulating SIRT3 in P53-Dependent Manner in Non-Small Cell Lung Cancer.

    PubMed

    Kumar, Ajay; Corey, Catherine; Scott, Iain; Shiva, Sruti; D'Cunha, Jonathan

    2016-01-01

    Minnelide/Triptolide (TL) has recently emerged as a potent anticancer drug in non-small cell lung cancer (NSCLC). However, the precise mechanism of its action remains ambiguous. In this study, we elucidated the molecular basis for TL-induced cell death in context to p53 status. Cell death was attributed to dysfunction of mitochondrial bioenergetics in p53-deficient cells, which was characterized by decreased mitochondrial respiration, steady-state ATP level and membrane potential, but augmented reactive oxygen species (ROS). Increased ROS production resulted in oxidative stress in TL-treated cells. This was exhibited by elevated nuclear levels of a redox-sensitive transcriptional factor, NF-E2-related factor-2 (NRF2), along with diminished cellular glutathione (GSH) content. We further demonstrated that in the absence of p53, TL blunted the expression of mitochondrial SIRT3 triggering increased acetylation of NDUAF9 and succinate dehydrogenase, components of complexes I and II of the electron transport chain (ETC). TL-mediated hyperacetylation of complexes I and II proteins and these complexes displayed decreased enzymatic activities. We also provide the evidence that P53 regulate steady-state level of SIRT3 through Proteasome-Pathway. Finally, forced overexpression of Sirt3, but not deacetylase-deficient mutant of Sirt3 (H243Y), restored the deleterious effect of TL on p53-deficient cells by rescuing mitochondrial bioenergetics. On contrary, Sirt3 deficiency in the background of wild-type p53 triggered TL-induced mitochondrial impairment that echoed TL effect in p53-deficeint cells. These findings illustrate a novel mechanism by which TL exerts its potent effects on mitochondrial function and ultimately the viability of NSCLC tumor. PMID:27501149

  16. Minnelide/Triptolide Impairs Mitochondrial Function by Regulating SIRT3 in P53-Dependent Manner in Non-Small Cell Lung Cancer

    PubMed Central

    Kumar, Ajay; Corey, Catherine; Scott, Iain; Shiva, Sruti; D’Cunha, Jonathan

    2016-01-01

    Minnelide/Triptolide (TL) has recently emerged as a potent anticancer drug in non-small cell lung cancer (NSCLC). However, the precise mechanism of its action remains ambiguous. In this study, we elucidated the molecular basis for TL-induced cell death in context to p53 status. Cell death was attributed to dysfunction of mitochondrial bioenergetics in p53-deficient cells, which was characterized by decreased mitochondrial respiration, steady-state ATP level and membrane potential, but augmented reactive oxygen species (ROS). Increased ROS production resulted in oxidative stress in TL-treated cells. This was exhibited by elevated nuclear levels of a redox-sensitive transcriptional factor, NF-E2-related factor-2 (NRF2), along with diminished cellular glutathione (GSH) content. We further demonstrated that in the absence of p53, TL blunted the expression of mitochondrial SIRT3 triggering increased acetylation of NDUAF9 and succinate dehydrogenase, components of complexes I and II of the electron transport chain (ETC). TL-mediated hyperacetylation of complexes I and II proteins and these complexes displayed decreased enzymatic activities. We also provide the evidence that P53 regulate steady-state level of SIRT3 through Proteasome-Pathway. Finally, forced overexpression of Sirt3, but not deacetylase-deficient mutant of Sirt3 (H243Y), restored the deleterious effect of TL on p53-deficient cells by rescuing mitochondrial bioenergetics. On contrary, Sirt3 deficiency in the background of wild-type p53 triggered TL-induced mitochondrial impairment that echoed TL effect in p53-deficeint cells. These findings illustrate a novel mechanism by which TL exerts its potent effects on mitochondrial function and ultimately the viability of NSCLC tumor. PMID:27501149

  17. Revival of impaired lung perfusion after sleeve lobectomy

    PubMed Central

    Shibano, Tomoki; Endo, Shunsuke; Yamamoto, Shinichi; Maki, Mitsuru

    2016-01-01

    Sleeve resection, a mainstay for centrally-located lung cancer, is a challenging procedure when the preserved lung is impaired. We herein reported a 61-year-old male who underwent right upper sleeve lobectomy for squamous cell carcinoma located at the orifice of the upper bronchus. The tumor invaded the main bronchus. A lung perfusion scan showed severe impairment, while the right middle and lower lobes were well expanded. Not only the spirogram, but also the lung perfusion in the residual lung, had markedly recovered at 2 months after the right upper extended sleeve lobectomy. The patient is currently living his normal daily life. Residual lung perfusion can be revived, even if it is impaired preoperatively. PMID:27076980

  18. Regulation of Immunoproteasome Function in the Lung

    PubMed Central

    Keller, Ilona E.; Vosyka, Oliver; Takenaka, Shinji; Kloß, Alexander; Dahlmann, Burkhardt; Willems, Lianne I.; Verdoes, Martijn; Overkleeft, Hermen S.; Marcos, Elisabeth; Adnot, Serge; Hauck, Stefanie M.; Ruppert, Clemens; Günther, Andreas; Herold, Susanne; Ohno, Shinji; Adler, Heiko; Eickelberg, Oliver; Meiners, Silke

    2015-01-01

    Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD). Disease progression is further exacerbated by pathogen infections due to impaired immune responses. Elimination of infected cells is achieved by cytotoxic CD8+  T cells that are activated by MHC I-mediated presentation of pathogen-derived antigenic peptides. The immunoproteasome, a specialized form of the proteasome, improves generation of antigenic peptides for MHC I presentation thereby facilitating anti-viral immune responses. However, immunoproteasome function in the lung has not been investigated in detail yet. In this study, we comprehensively characterized the function of immunoproteasomes in the human and murine lung. Parenchymal cells of the lung express low constitutive levels of immunoproteasomes, while they are highly and specifically expressed in alveolar macrophages. Immunoproteasome expression is not altered in whole lung tissue of COPD patients. Novel activity-based probes and native gel analysis revealed that immunoproteasome activities are specifically and rapidly induced by IFNγ treatment in respiratory cells in vitro and by virus infection of the lung in mice. Our results suggest that the lung is potentially capable of mounting an immunoproteasome-mediated efficient adaptive immune response to intracellular infections. PMID:25989070

  19. Lacking power impairs executive functions.

    PubMed

    Smith, Pamela K; Jostmann, Nils B; Galinsky, Adam D; van Dijk, Wilco W

    2008-05-01

    Four experiments explored whether lacking power impairs executive functioning, testing the hypothesis that the cognitive presses of powerlessness increase vulnerability to performance decrements during complex executive tasks. In the first three experiments, low power impaired performance on executive-function tasks: The powerless were less effective than the powerful at updating (Experiment 1), inhibiting (Experiment 2), and planning (Experiment 3). Existing research suggests that the powerless have difficulty distinguishing between what is goal relevant and what is goal irrelevant in the environment. A fourth experiment established that the executive-function impairment associated with low power is driven by goal neglect. The current research implies that the cognitive alterations arising from powerlessness may help foster stable social hierarchies and that empowering employees may reduce costly organizational errors. PMID:18466404

  20. A model of low-level primary blast brain trauma results in cytoskeletal proteolysis and chronic functional impairment in the absence of lung barotrauma.

    PubMed

    Park, Eugene; Gottlieb, James J; Cheung, Bob; Shek, Pang N; Baker, Andrew J

    2011-03-01

    Shock-wave exposure from improvised explosive devices (IEDs) has been implicated as a possible contributing factor to neurological impairment reported in combat veterans. However, evidence-based substantiation of this implication, particularly for low-level exposure in the absence of external signs of trauma, remain elusive. Accordingly, we constructed an open-ended shock tube producing a short-duration, low-amplitude shockwave. Low-level (11.5 kPa static overpressure) complex shock-wave exposure in rats resulted in no histological evidence of lung injury. By contrast, delayed cytoskeletal proteolysis of αII-spectrin was detected in the cortex and hippocampus by 12 h post-injury. Cell death was minimal and localized predominantly in the corpus callosum and periventricular regions. These regions, with presumably different density interfaces, exhibit biological responses to shockwaves consistent with interface turbulence described by Richtmyer-Meshkov instability. Evoked compound action potential (CAP) recordings from the corpus callosum showed a significant increase in the duration of CAP responses at 14 and 30 days post-injury, and a gradual depression in the unmyelinated fiber amplitude. Shielding the head attenuated αII-spectrin cytoskeletal breakdown, thus directly implicating low-level shock-wave exposure as a cause of brain injury in the rat. Despite anatomical and scaling differences in rats compared to humans, the results suggest the potential for undiagnosed traumatic brain pathologies occurring in combat veterans following shock-wave exposure. PMID:21142686

  1. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation

    PubMed Central

    Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R.; D’Alessio, Franco R.; Lambert, Allison A.; Kirk, Gregory; Blankson, Joel; Drummond, M. Bradley; Tsibris, Athe M.

    2016-01-01

    epithelial cells and alter their function by impairing cell-cell adhesion and increasing the expression of inflammatory mediators. These observed changes may contribute local inflammation, which can lead to lung function decline and increased susceptibility to COPD in HIV patients. PMID:26930653

  2. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    PubMed

    Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

    2016-01-01

    epithelial cells and alter their function by impairing cell-cell adhesion and increasing the expression of inflammatory mediators. These observed changes may contribute local inflammation, which can lead to lung function decline and increased susceptibility to COPD in HIV patients. PMID:26930653

  3. Lung function after bone marrow grafting

    SciTech Connect

    Depledge, M.H.; Barrett, A.; Powles, R.L.

    1983-02-01

    Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (D/sub L/CO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

  4. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  5. Functional impairment in social anxiety disorder.

    PubMed

    Aderka, Idan M; Hofmann, Stefan G; Nickerson, Angela; Hermesh, Haggai; Gilboa-Schechtman, Eva; Marom, Sofi

    2012-04-01

    The present study examined functional impairment among treatment seekers with social anxiety disorder (SAD). We investigated the effects of diagnostic subtypes of SAD and comorbidity with mood and anxiety disorders on impairment. In addition, we used cluster analysis procedures to empirically identify subgroups of individuals with distinct patterns of impairment. Participants were 216 treatment-seeking individuals with SAD. Clinical interviews were undertaken to determine diagnoses of anxiety disorders and major depressive disorder, and a battery of self-report measures was administered to index symptoms of social anxiety, depression and extent of impairment. Results indicated that individuals with the generalized subtype of SAD had greater impairment in all three life domains compared to individuals with the nongeneralized subtype. Comorbidity with mood disorders was associated with greater impairment than SAD alone, but comorbidity with anxiety disorders was not. Four distinct impairment profiles emerged from the cluster analysis: primary work/studies impairment, primary social life impairment, both work/studies and social impairment, and impairment in all domains. Findings from this study suggest that SAD is associated with substantial impairment across multiple domains, and that individuals with SAD present diverse impairment profiles. These profiles may inform subtyping of the disorder as well as therapeutic interventions. PMID:22306132

  6. 38 CFR 4.10 - Functional impairment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Functional impairment. 4.10 Section 4.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES General Policy in Rating § 4.10 Functional impairment. The basis of disability evaluations is the ability of the body as a...

  7. Lung function in insulation workers.

    PubMed Central

    Clausen, J; Netterstrøm, B; Wolff, C

    1993-01-01

    To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID:8457492

  8. Marital Conflict, Depressive Symptoms, and Functional Impairment

    PubMed Central

    Choi, Heejeong; Marks, Nadine F.

    2008-01-01

    Guided by a stress process perspective, we investigated (a) whether marital conflict might directly lead to changes in depression and functional impairment, (b) whether marital conflict might indirectly lead to changes in functional impairment via depression, and (c) whether marital conflict might indirectly lead to changes in depression via functional impairment. We estimated a latent variable causal model using 3 waves of data from the National Survey of Families and Households (N = 1,832). Results indicated that marital conflict directly led to increases in depression and functional impairment and indirectly led to a rise in depression via functional impairment. Overall, findings suggest marital conflict is a significant risk factor for psychological and physical health among midlife and older adults. PMID:18698378

  9. Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.

    PubMed

    Erickson, John J; Rogers, Meredith C; Tollefson, Sharon J; Boyd, Kelli L; Williams, John V

    2016-07-01

    Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID:27259857

  10. Inferential functioning in visually impaired children.

    PubMed

    Puche-Navarro, Rebeca; Millán, Rafael

    2007-01-01

    The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children perform slightly better in the use of inductive and relational inferences in the verbal format, while in the manipulative format children with normal sight perform better. These results suggest that in inferential functioning of young children, and especially visually impaired children, the format of the task influences performance more than the child's visual ability. PMID:16647837

  11. Functional impairment in progressive supranuclear palsy

    PubMed Central

    Gerstenecker, Adam; Litvan, Irene

    2013-01-01

    Objective: The current study sought to describe the functional profiles of patients with early-stage progressive supranuclear palsy (PSP) in a large prospective, multisite study. Methods: Using data from 202 individuals meeting criteria for clinically definite or probable PSP, 3 functional scales were examined. Functional scores were then compared to measures of motor, cognition, and psychiatric symptoms. Results: Functional disability was high in early-stage PSP, with 100% of patients having less than perfect scores on all functional scales. Whereas functional scores tended not to be related to cognition or psychiatric symptoms, they were strongly related to motoric ratings. Conclusions: Both clinically and in research settings, the definition of functional intactness/impairment has important implications. Future studies should examine if functional impairment is this high in PSP or if new scales of functional abilities need to be developed for this condition. PMID:23303854

  12. Functional respiratory assessment in interstitial lung disease.

    PubMed

    Miguel-Reyes, José Luis; Gochicoa-Rangel, Laura; Pérez-Padilla, Rogelio; Torre-Bouscoulet, Luis

    2015-01-01

    Interstitial lung diseases are a heterogeneous group of disorders that affect, to a greater or lesser degree, the alveolus, peripheral airway, and septal interstitium. Functional assessment in patients suspected of having an interstitial lung disease has implications for diagnosis and makes it possible to objectively analyze both response to treatment and prognosis. Recently the clinical value of lung-diffusing capacity and the six-minute walking test has been confirmed, and these are now important additions to the traditional assessment of lung function that is based on spirometry. Here we review the state-of-the-art methods for the assessment of patients with interstitial lung disease. PMID:25857578

  13. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.

    PubMed

    Pezzulo, Alejandro A; Tang, Xiao Xiao; Hoegger, Mark J; Alaiwa, Mahmoud H Abou; Ramachandran, Shyam; Moninger, Thomas O; Karp, Phillip H; Wohlford-Lenane, Christine L; Haagsman, Henk P; van Eijk, Martin; Bánfi, Botond; Horswill, Alexander R; Stoltz, David A; McCray, Paul B; Welsh, Michael J; Zabner, Joseph

    2012-07-01

    Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO(3)(-) transport. Without CFTR, airway epithelial HCO(3)(-) secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions. PMID:22763554

  14. Kinase Impaired BRAF Mutations Confer Lung Cancer Sensitivity to Dasatinib

    PubMed Central

    Sen, Banibrata; Peng, Shaohua; Tang, Ximing; Erickson, Heidi S.; Galindo, Hector; Mazumdar, Tuhina; Stewart, David J.; Wistuba, Ignacio; Johnson, Faye M.

    2013-01-01

    During a clinical trial of the tyrosine kinase inhibitor dasatinib for advanced non–small cell lung cancer (NSCLC) one patient responded dramatically and remains cancer-free 4 years later. A comprehensive analysis of his tumor revealed a previously undescribed, kinase inactivating BRAF mutation (Y472CBRAF); no inactivating BRAF mutations were found in the non-responding tumors taken from other patients. Cells transfected with Y472CBRAF exhibited CRAF, MEK, and ERK activation – characteristics identical to signaling changes that occur with previously known kinase inactivating BRAF mutants. Dasatinib selectively induced senescence in NSCLC cells with inactivating BRAF mutations. Transfection of other NSCLC cells with these BRAF mutations also increased these cells’ dasatinib sensitivity, whereas transfection with an activating BRAF mutation led to their increased dasatinib resistance. The sensitivity induced by Y472CBRAF was reversed by the introduction of a BRAF mutation that impairs RAF dimerization. Dasatinib inhibited CRAF modestly, but concurrently induced RAF dimerization resulting in ERK activation in NSCLC cells with kinase inactivating BRAF mutations. The sensitivity of NSCLC with kinase impaired BRAF to dasatinib suggested synthetic lethality of BRAF and a dasatinib target. Inhibiting BRAF in NSCLC cells expressing wild-type BRAF likewise enhanced these cells’ dasatinib sensitivity. Thus, the patient’s BRAF mutation was likely responsible for his tumor’s marked response to dasatinib, suggesting that tumors bearing kinase impaired BRAF mutations may be exquisitely sensitive to dasatinib. Moreover, the potential synthetic lethality of combination therapy including dasatinib and BRAF inhibitors may lead to additional therapeutic options against cancers with wild-type BRAF. PMID:22649091

  15. Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats.

    PubMed

    Cannon, Daniel T; Liu, Jie; Sakurai, Reiko; Rossiter, Harry B; Rehan, Virender K

    2016-04-01

    Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARγ pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARγ receptor agonist). Sprague-Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg(-1)), or NIC + RGZ (3 mg kg(-1)) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 ± 0.8 and 4.1 ± 1.4 vs. 8.8 ± 2.5 pmol s mg(-1); p < 0.05). The respiratory control ratio for ADP, an index of mitochondrial coupling, was reduced in NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation. PMID:26899624

  16. Loss of Mitochondrial Function Impairs Lysosomes.

    PubMed

    Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

    2016-05-01

    Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. PMID:26987902

  17. Reduced Airway Surface pH Impairs Bacterial Killing in the Porcine Cystic Fibrosis Lung

    PubMed Central

    Pezzulo, Alejandro A.; Tang, Xiao Xiao; Hoegger, Mark J.; Abou Alaiwa, Mahmoud H.; Ramachandran, Shyam; Moninger, Thomas O.; Karp, Phillip H.; Wohlford-Lenane, Christine L.; Haagsman, Henk P.; van Eijk, Martin; Bánfi, Botond; Horswill, Alexander R.; Stoltz, David A.; McCray, Paul B.; Welsh, Michael J.; Zabner, Joseph

    2012-01-01

    Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 1. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how loss of CFTR first disrupts airway host defense has remained uncertain 2–6. We asked what abnormalities impair eradication when a bacterium lands on the pristine surface of a newborn CF airway? To investigate these defects, we interrogated the viability of individual bacteria immobilized on solid grids and placed on the airway surface. As a model we studied CF pigs, which spontaneously develop hallmark features of CF lung disease 7,8. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria 8. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly killed bacteria in vivo, when removed from the lung, and in primary epithelial cultures. Lack of CFTR reduced bacterial killing. We found that ASL pH was more acidic in CF, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defense defect to loss of CFTR, an anion channel that facilitates HCO3− transport 9–13. Without CFTR, airway epithelial HCO3− secretion is defective, ASL pH falls and inhibits antimicrobial function, and thereby impairs killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF and that assaying bacterial killing could report on the benefit of therapeutic interventions. PMID:22763554

  18. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... caused by conditions such as pulmonary fibrosis and sarcoidosis (sar-koy-DOE-sis). Also, these tests might ...

  19. Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study

    PubMed Central

    Wozniak, Amy W.; Hough, Catherine L.; Morris, Peter E.; Dinglas, Victor D.; Jackson, James C.; Mendez-Tellez, Pedro A.; Shanholtz, Carl; Ely, E. Wesley; Colantuoni, Elizabeth

    2014-01-01

    Rationale: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. Objectives: To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization. Methods: A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness–related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. Measurements and Main Results: At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes. Conclusions: Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors’ physical outcomes. PMID:24716641

  20. Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

    PubMed Central

    2011-01-01

    Background Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis. Methods MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA. Results Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung. Conclusions These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures. PMID:21851604

  1. Respiratory and lower limb muscle function in interstitial lung disease.

    PubMed

    Panagiotou, Marios; Polychronopoulos, Vlasis; Strange, Charlie

    2016-05-01

    Growing evidence suggests that respiratory and limb muscle function may be impaired in patients with interstitial lung disease (ILD). Importantly, muscle dysfunction could promote dyspnoea, fatigue and functional limitation all of which are cardinal features of ILD. This article examines the risk factors for skeletal muscle dysfunction in ILD, reviews the current evidence on overall respiratory and limb muscle function and focuses on the occurrence and implications of skeletal muscle dysfunction in ILD. Research limitations and pathways to address the current knowledge gaps are highlighted. PMID:26768011

  2. Rehabilitation of impaired speech function (dysarthria, dysglossia)

    PubMed Central

    Schröter-Morasch, Heidrun; Ziegler, Wolfram

    2005-01-01

    Speech disorders can result (1) from sensorimotor impairments of articulatory movements = dysarthria, or (2) from structural changes of the speech organs, in adults particularly after surgical and radiochemical treatment of tumors = dysglossia. The decrease of intelligibility, a reduced vocal stamina, the stigmatization of a conspicuous voice and manner of speech, the reduction of emotional expressivity all mean greatly diminished quality of life, restricted career opportunities and diminished social contacts. Intensive therapy based on the pathophysiological facts is absolutely essential: Functional exercise therapy plays a central role; according to symptoms and their progression it can be complemented with prosthetic and surgical approaches. In severe cases communicational aids have to be used. All rehabilitation measures have to take account of frequently associated disorders of body motor control and/or impairment of cognition and behaviour. PMID:22073063

  3. Lung function in sickle cell disease.

    PubMed

    Koumbourlis, Anastassios C

    2014-03-01

    Although some of the most severe complications of Sickle Cell Disease (SCD) tend to be acute and severe (e.g. acute chest syndrome, stroke etc.), the chronic ones can be equally debilitating. Prominent among them is the effect that the disease has on lung growth and function. For many years the traditional teaching has been that SCD is associated with the development of a restrictive lung defect. However, there is increasing evidence that this is not a universal finding and that at least during childhood and adolescence, the majority of the patients have a normal or obstructive pattern of lung function. The following article reviews the current knowledge on the effects of SCD on lung growth and function. Special emphasis is given to the controversies among the published articles in the literature and discusses possible causes for these discrepancies. PMID:24268618

  4. Functional Hubs in Mild Cognitive Impairment

    NASA Astrophysics Data System (ADS)

    Navas, Adrián; Papo, David; Boccaletti, Stefano; Del-Pozo, F.; Bajo, Ricardo; Maestú, Fernando; Martínez, J. H.; Gil, Pablo; Sendiña-Nadal, Irene; Buldú, Javier M.

    We investigate how hubs of functional brain networks are modified as a result of mild cognitive impairment (MCI), a condition causing a slight but noticeable decline in cognitive abilities, which sometimes precedes the onset of Alzheimer's disease. We used magnetoencephalography (MEG) to investigate the functional brain networks of a group of patients suffering from MCI and a control group of healthy subjects, during the execution of a short-term memory task. Couplings between brain sites were evaluated using synchronization likelihood, from which a network of functional interdependencies was constructed and the centrality, i.e. importance, of their nodes was quantified. The results showed that, with respect to healthy controls, MCI patients were associated with decreases and increases in hub centrality respectively in occipital and central scalp regions, supporting the hypothesis that MCI modifies functional brain network topology, leading to more random structures.

  5. Functional magnetic resonance imaging of the lung.

    PubMed

    Biederer, J; Heussel, C P; Puderbach, M; Wielpuetz, M O

    2014-02-01

    Beyond being a substitute for X-ray, computed tomography, and scintigraphy, magnetic resonance imaging (MRI) inherently combines morphologic and functional information more than any other technology. Lung perfusion: The most established method is first-pass contrast-enhanced imaging with bolus injection of gadolinium chelates and time-resolved gradient-echo (GRE) sequences covering the whole lung (1 volume/s). Images are evaluated visually or semiquantitatively, while absolute quantification remains challenging due to the nonlinear relation of T1-shortening and contrast material concentration. Noncontrast-enhanced perfusion imaging is still experimental, either based on arterial spin labeling or Fourier decomposition. The latter is used to separate high- and low-frequency oscillations of lung signal related to the effects of pulsatile blood flow. Lung ventilation: Using contrast-enhanced first-pass perfusion, lung ventilation deficits are indirectly identified by hypoxic vasoconstriction. More direct but still experimental approaches use either inhalation of pure oxygen, an aerosolized contrast agent, or hyperpolarized noble gases. Fourier decomposition MRI based on the low-frequency lung signal oscillation allows for visualization of ventilation without any contrast agent. Respiratory mechanics: Time-resolved series with high background signal such as GRE or steady-state free precession visualize the movement of chest wall, diaphragm, mediastinum, lung tissue, tracheal wall, and tumor. The assessment of volume changes allows drawing conclusions on regional ventilation. With this arsenal of functional imaging capabilities at high spatial and temporal resolution but without radiation burden, MRI will find its role in regional functional lung analysis and will therefore overcome the sensitivity of global lung function analysis for repeated short-term treatment monitoring. PMID:24481761

  6. The Pseudomonas aeruginosa exoenzyme Y impairs endothelial cell proliferation and vascular repair following lung injury.

    PubMed

    Stevens, Trevor C; Ochoa, Cristhiaan D; Morrow, K Adam; Robson, Matthew J; Prasain, Nutan; Zhou, Chun; Alvarez, Diego F; Frank, Dara W; Balczon, Ron; Stevens, Troy

    2014-05-15

    Exoenzyme Y (ExoY) is a Pseudomonas aeruginosa toxin that is introduced into host cells through the type 3 secretion system (T3SS). Once inside the host cell cytoplasm, ExoY generates cyclic nucleotides that cause tau phosphorylation and microtubule breakdown. Microtubule breakdown causes interendothelial cell gap formation and tissue edema. Although ExoY transiently induces interendothelial cell gap formation, it remains unclear whether ExoY prevents repair of the endothelial cell barrier. Here, we test the hypothesis that ExoY intoxication impairs recovery of the endothelial cell barrier following gap formation, decreasing migration, proliferation, and lung repair. Pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains for 6 h, including one possessing an active ExoY (PA103 exoUexoT::Tc pUCPexoY; ExoY(+)), one with an inactive ExoY (PA103ΔexoUexoT::Tc pUCPexoY(K81M); ExoY(K81M)), and one that lacks PcrV required for a functional T3SS (ΔPcrV). ExoY(+) induced interendothelial cell gaps, whereas ExoY(K81M) and ΔPcrV did not promote gap formation. Following gap formation, bacteria were removed and endothelial cell repair was examined. PMVECs were unable to repair gaps even 3-5 days after infection. Serum-stimulated growth was greatly diminished following ExoY intoxication. Intratracheal inoculation of ExoY(+) and ExoY(K81M) caused severe pneumonia and acute lung injury. However, whereas the pulmonary endothelial cell barrier was functionally improved 1 wk following ExoY(K81M) infection, pulmonary endothelium was unable to restrict the hyperpermeability response to elevated hydrostatic pressure following ExoY(+) infection. In conclusion, ExoY is an edema factor that chronically impairs endothelial cell barrier integrity following lung injury. PMID:24705722

  7. Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

    2015-11-01

    Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer. PMID:26618048

  8. Respiratory sequelae and lung function after whooping cough in infancy.

    PubMed Central

    Krantz, I; Bjure, J; Claesson, I; Eriksson, B; Sixt, R; Trollfors, B

    1990-01-01

    The lung function of 31 children, aged 6-13 years, who had whooping cough as infants and 32 control children matched for age, sex, and residence area were compared in a community based cohort study. Family history of obstructive airway disease, smoking habits in the family, atopy, and other background factors examined were similar in the two groups. The ratios of recalled repeated acute respiratory infections did not differ among the groups. Children in the control group were slightly more involved in physical activities. History of obstructive airway disease, findings on chest radiography, and distribution of immunoglobulin concentrations, including IgE, did not differ significantly. Lung function before and after exercise and after inhalation of salbutamol were not different. No impairment of small airways was detected. Our data do not support the hypothesis that whooping cough in itself is a causal factor for later obstructive respiratory disease. PMID:2378512

  9. Does acute exposure to aldehydes impair pulmonary function and structure?

    PubMed

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group. PMID:27102012

  10. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    PubMed

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  11. Does lung diffusion impairment affect exercise capacity in patients with heart failure?

    PubMed Central

    Agostoni, P G; Bussotti, M; Palermo, P; Guazzi, M

    2002-01-01

    Objective: To determine whether there is a relation between impairment of lung diffusion and reduced exercise capacity in chronic heart failure. Design: 40 patients with heart failure in stable clinical condition and 40 controls participated in the study. All subjects underwent standard pulmonary function tests plus measurements of resting lung diffusion (carbon monoxide transfer, Tlco), pulmonary capillary volume (Vc), and membrane resistance (Dm), and maximal cardiopulmonary exercise testing. In 20 patients and controls, the following investigations were also done: (1) resting and constant work rate Tlco; (2) maximal cardiopulmonary exercise testing with inspiratory O2 fractions of 0.21 and 0.16; and (3) rest and peak exercise blood gases. The other subjects underwent Tlco, Dm, and Vc measurements during constant work rate exercise. Results: In normoxia, exercise induced reductions of haemoglobin O2 saturation never occurred. With hypoxia, peak exercise uptake (peak V̇o2) decreased from (mean (SD)) 1285 (395) to 1081 (396) ml/min (p < 0.01) in patients, and from 1861 (563) to 1771 (457) ml/min (p < 0.05) in controls. Resting Tlco correlated with peak V̇o2 in heart failure (normoxia < hypoxia). In heart failure patients and normal subjects, Tlco and peak V̇o2 correlated with O2 arterial content at rest and during peak exercise in both normoxia and hypoxia. Tlco, Vc, and Dm increased during exercise. The increase in Tlco was greater in patients who had a smaller reduction of exercise capacity with hypoxia. Alveolar–arterial O2 gradient at peak correlated with exercise capacity in heart failure during normoxia and, to a greater extent, during hypoxia. Conclusions: Lung diffusion impairment is related to exercise capacity in heart failure. PMID:12381630

  12. Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline

    PubMed Central

    Lai, Peggy S.; Hang, Jing-qing; Zhang, Feng-ying; Sun, J.; Zheng, Bu-Yong; Su, Li; Washko, George R.; Christiani, David C.

    2016-01-01

    Background: Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined. Objective: We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT). Methods: The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis. Results: Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (–1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation –1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (–6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011. Conclusions: There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of

  13. Claudins: Gatekeepers of lung epithelial function.

    PubMed

    Schlingmann, Barbara; Molina, Samuel A; Koval, Michael

    2015-06-01

    The lung must maintain a proper barrier between airspaces and fluid filled tissues in order to maintain lung fluid balance. Central to maintaining lung fluid balance are epithelial cells which create a barrier to water and solutes. The barrier function of these cells is mainly provided by tight junction proteins known as claudins. Epithelial barrier function varies depending on the different needs within the segments of the respiratory tree. In the lower airways, fluid is required to maintain mucociliary clearance, whereas in the terminal alveolar airspaces a thin layer of surfactant enriched fluid lowers surface tension to prevent airspace collapse and is critical for gas exchange. As the epithelial cells within the segments of the respiratory tree differ, the composition of claudins found in these epithelial cells is also different. Among these differences is claudin-18 which is uniquely expressed by the alveolar epithelial cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously expressed throughout the respiratory epithelium. Claudin-5 is expressed by both pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model systems and histologic analysis of lungs from human patients, roles for specific claudins in maintaining barrier function and protecting the lung from the effects of acute injury and disease are being identified. One surprising finding is that claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond simply maintaining a selective paracellular permeability barrier. This suggests claudins have more nuanced roles for the control of airway and alveolar physiology in the healthy and diseased lung. PMID:25951797

  14. Lung Extracellular Matrix and Fibroblast Function

    PubMed Central

    2015-01-01

    Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by virtue of the contextual clues it imparts to cells. Qualities including dimensionality, molecular composition, and intrinsic stiffness all promote normal function of the lung ECM. Alterations in composition and/or modulation of stiffness of the focally injured or diseased lung ECM microenvironment plays a part in reparative processes performed by fibroblasts. Under conditions of remodeling or in disease states, inhomogeneous stiffening (or softening) of the pathologic ECM may both precede modifications in cell behavior and be a result of disease progression. The ability of ECM to stimulate further ECM production by fibroblasts and drive disease progression has potentially significant implications for mesenchymal stromal cell–based therapies; in the setting of pathologic ECM stiffness or composition, the therapeutic intent of progenitor cells may be subverted. Taken together, current data suggest that lung ECM actively contributes to health and disease; thus, mediators of cell–ECM signaling or factors that influence ECM stiffness may represent viable therapeutic targets in many lung disorders. PMID:25830832

  15. Divers' lung function: small airways disease?

    PubMed Central

    Thorsen, E; Segadal, K; Kambestad, B; Gulsvik, A

    1990-01-01

    Pulmonary function was measured in 152 professional saturation divers and in a matched control group of 106 subjects. Static lung volumes, dynamic lung volumes and flows, transfer factor for carbon monoxide (T1CO), transfer volume per unit alveolar volume (KCO), delta-N2, and closing volume (CV) were measured and compared with reference values from recent Scandinavian studies, British submariners, and the European Community for Coal and Steel (ECCS) recommended reference values. Diving exposure was assessed as years of diving experience, total number of days in saturation and depth, and as the product of days in saturation and mean depth. Divers had significantly lower values for forced expired volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, FEF25-75%, FEF75-85%, FEF50%, FEF75%, T1CO, and KCO compared with the controls and a significantly higher CV. There was a positive correlation between diving exposure and CV, whereas the other variables had negative correlations with diving exposure. Values for the control group were not different from the predictive values of Scandinavian reference studies or British submariners, although the ECCS standard predicted significantly lower values for the lung function variables both in divers and the control group. The pattern of the differences in lung function variables between the divers and controls is consistent with small airways dysfunction and with the transient changes in lung function found immediately after a single saturation dive. The association between reduced pulmonary function and previous diving exposure further indicates the presence of cumulative long term effects of diving on pulmonary function. PMID:2393630

  16. Annual Research Review: Conceptualising Functional Impairment in Children and Adolescents

    ERIC Educational Resources Information Center

    Rapee, Ronald M.; Bogels, Susan M.; van der Sluis, Cathy M.; Craske, Michelle G.; Ollendick, Thomas

    2012-01-01

    Functional impairment is a key factor in the clinical importance of mental health problems in children. Yet, the nature of impairment and criteria for defining and assessing impairment in childhood disorders has been surprisingly overlooked in much of the literature. The current article examines the extant literature on the conceptualisation,…

  17. Functional impairments due to unilateral deafness.

    PubMed

    Welsh, Louis W; Welsh, John J; Rosen, Laurie F; Dragonette, Joseph E

    2004-12-01

    The authors investigated the impact of unilateral listening upon two central auditory functions: speech discrimination in a noisy environment, and the ability to process and clearly recognize modestly accelerated speech by 30% compression (shortened exposure). We determined that the negative impact of listening to speech in the milieu of noise was individually variable. The data revealed a wide range of impairment, from mild to relatively severe (ie, 0% to 60% [mean, 34%]; normative data, 4% to 36% [mean, 14%]). The performance scores for recognition of compressed sentences were not markedly influenced by unilateral deafness, but the functional results of the residual ear were correlated with a loss of high-frequency sensitivity (mean of 54% correct in severe unilateral deafness with an associated high-frequency loss versus 93% correct in normal controls). Reorganization of the central nervous system by "plasticity" or biological maturation over time failed to improve the performance of monaural listening. The currently recommended methods of remediation for this sensory deficit are discussed, and newer technologies under investigation are examined. PMID:15633902

  18. LUNG FUNCTION AND ITS GROWTH

    EPA Science Inventory

    Evidence that certain uncomplicated upper respiratory infections (URI) induce pulmonary function abnormalities in adults prompted a study in children where such infections occur more frequently. In a longitudinal study, 55 children aged 2.5-9 years were observed for a mean durati...

  19. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  20. JWH-018 impairs sensorimotor functions in mice.

    PubMed

    Ossato, A; Vigolo, A; Trapella, C; Seri, C; Rimondo, C; Serpelloni, G; Marti, M

    2015-08-01

    Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a synthetic cannabinoid agonist illegally marketed in "Spice" and "herbal blend" for its psychoactive effect greater than those produced by cannabis. In rodents JWH-018 reproduces typical effects of (-)-Δ(9)-THC or Dronabinol® (Δ(9)-THC) such as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on sensorimotor functions are still unknown. Therefore, the aim of the present study is to investigate the effect of acute administration of JWH-018 (0.01-6mg/kg i.p.) on sensorimotor functions in male CD-1 mice and to compare its effects with those caused by the administration of Δ(9)-THC (0.01-6mg/kg i.p.). A specific battery of behavioral tests were adopted to investigate effects of cannabinoid agonists on sensorimotor functions (visual, auditory, tactile) and neurological changes (convulsion, myoclonia, hyperreflexia) while video-tracking analysis was used to study spontaneous locomotion. JWH-018 administration inhibited sensorimotor responses at lower doses (0.01-0.1mg/kg), reduced spontaneous locomotion at intermediate/high doses (1-6mg/kg) and induced convulsions, myoclonia and hyperreflexia at high doses (6mg/kg). Similarly, administration of Δ(9)-THC reduced sensorimotor responses in mice but it did not inhibit spontaneous locomotion and it did not induce neurological alterations. All behavioral effects and neurological alterations were prevented by the administration of the selective CB1 receptor antagonist/inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM 251). For the first time these data demonstrate that JWH-018 impairs sensorimotor responses in mice. This aspect should be carefully evaluated to better understand the potential danger that JWH-018 may pose to public health, with particular reference to decreased performance in driving and hazardous works. PMID:25987201

  1. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    SciTech Connect

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Gonzalez-De Alba, Cesar; Froines, John R.; Espinosa-Fematt, Jorge A.

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  2. Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation

    EPA Science Inventory

    A single ozone exposure causes pulmonary injury and systemic metabolic alterations through neuronal and hypothalamus pituitary adrenal axis activation. Metabolically impaired Goto Kakizaki (GK) rats with non-obese type-2 diabetes are more sensitive to ozone induced changes than h...

  3. Hyperglycemia Impairs Proteasome Function by Methylglyoxal

    PubMed Central

    Queisser, Markus A.; Yao, Dachun; Geisler, Sven; Hammes, Hans-Peter; Lochnit, Günter; Schleicher, Erwin D.; Brownlee, Michael; Preissner, Klaus T.

    2010-01-01

    OBJECTIVE The ubiquitin-proteasome system is the main degradation machinery for intracellularly altered proteins. Hyperglycemia has been shown to increase intracellular levels of the reactive dicarbonyl methylglyoxal (MGO) in cells damaged by diabetes, resulting in modification of proteins and alterations of their function. In this study, the influence of MGO-derived advanced glycation end product (AGE) formation on the activity of the proteasome was investigated in vitro and in vivo. RESEARCH DESIGN AND METHODS MGO-derived AGE modification of proteasome subunits was analyzed by mass spectrometry, immunoprecipitation, and Western blots. Proteasome activity was analyzed using proteasome-specific fluorogenic substrates. Experimental models included bovine retinal endothelial cells, diabetic Ins2Akita mice, glyoxalase 1 (GLO1) knockdown mice, and streptozotocin (STZ)-injected diabetic mice. RESULTS In vitro incubation with MGO caused adduct formation on several 20S proteasomal subunit proteins. In cultured endothelial cells, the expression level of the catalytic 20S proteasome subunit was not altered but proteasomal chymotrypsin-like activity was significantly reduced. In contrast, levels of regulatory 19S proteasomal proteins were decreased. In diabetic Ins2Akita, STZ diabetic, and nondiabetic and diabetic G101 knockdown mice, chymotrypsin-like activity was also reduced and MGO modification of the 20S-β2 subunit was increased. CONCLUSIONS Hyperglycemia-induced formation of MGO covalently modifies the 20S proteasome, decreasing its activity in the diabetic kidney and reducing the polyubiquitin receptor 19S-S5a. The results indicate a new link between hyperglycemia and impairment of cell functions. PMID:20009088

  4. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    PubMed Central

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

    2016-01-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

  5. Lung function changes in wildland firefighters working at prescribed burns.

    SciTech Connect

    Adetona, Olorunfemi; Hall, Daniel, B.; Naeher, L,P.

    2011-10-01

    Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.

  6. Cognitive Function, Mental Health, and Health-related Quality of Life after Lung Transplantation

    PubMed Central

    Cohen, David G.; Christie, Jason D.; Anderson, Brian J.; Diamond, Joshua M.; Judy, Ryan P.; Shah, Rupal J.; Cantu, Edward; Bellamy, Scarlett L.; Blumenthal, Nancy P.; Demissie, Ejigayehu; Hopkins, Ramona O.

    2014-01-01

    Rationale: Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited. Objectives: Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation. Methods: In a retrospective cohort study, we assessed cognitive function, mental health, and health-related quality of life using a validated battery of standardized tests in 42 subjects post-transplantation. The battery assessed cognition, depression, anxiety, resilience, and post-traumatic stress disorder (PTSD). Cognitive function was assessed using the Montreal Cognitive Assessment, a validated screening test with a range of 0 to 30. We hypothesized that cognitive function post-transplantation would be associated with type of transplant, cardiopulmonary bypass, primary graft dysfunction, allograft ischemic time, and physical therapy post-transplantation. We used multivariable linear regression to examine the relationship between candidate risk factors and cognitive function post-transplantation. Measurements and Main Results: Mild cognitive impairment (score, 18–25) was observed in 67% of post-transplant subjects (95% confidence interval [CI]: 50–80%) and moderate cognitive impairment (score, 10–17) was observed in 5% (95% CI, 1–16%) of post-transplant subjects. Symptoms of moderate to severe anxiety and depression were observed in 21 and 3% of post-transplant subjects, respectively. No transplant recipients reported symptoms of PTSD. Higher resilience correlated with less psychological distress in the domains of depression (P < 0.001) and PTSD (P = 0.02). Prolonged graft ischemic time was independently associated with worse cognitive performance after lung transplantation (P = 0.001). The functional gain in 6-minute-walk distance achieved at the end of post

  7. Impaired immune function in Gulf War Illness

    PubMed Central

    Whistler, Toni; Fletcher, Mary Ann; Lonergan, William; Zeng, Xiao-R; Lin, Jin-Mann; LaPerriere, Arthur; Vernon, Suzanne D; Klimas, Nancy G

    2009-01-01

    Background Gulf War Illness (GWI) remains a serious health consequence for at least 11,000 veterans of the first Gulf War in the early 1990s. Our understanding of the health consequences that resulted remains inadequate, and this is of great concern with another deployment to the same theater of operations occurring now. Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling. Methods This pilot study enrolled 9 GWI cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age. We measured peripheral blood cell numbers, NK cytotoxicity, cytokines and expression levels of 20,000 genes immediately before, immediately after and 4 hours following a standard bicycle ergometer exercise challenge. Results A repeated-measures analysis of variance revealed statistically significant differences for three NK cell subsets and NK cytotoxicity between cases and controls (p < 0.05). Linear regression analysis correlating NK cell numbers to the gene expression profiles showed high correlation of genes associated with NK cell function, serving as a biologic validation of both the in vitro assays and the microarray platform. Intracellular perforin levels in NK and CD8 T-cells trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene PRF1. Genes distinguishing cases from controls were associated with the glucocorticoid signaling pathway. Conclusion GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro

  8. Lung Function Monitoring; A Randomized Agreement Study

    PubMed Central

    Berntsen, Sveinung; Stølevik, Solvor B.; Mowinckel, Petter; Nystad, Wenche; Stensrud, Trine

    2016-01-01

    Objective: To determine the agreement between devices and repeatability within devices of the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and forced expiratory flow at 50% of FVC (FEF50) values measured using the four spirometers included in the study. Methods: 50 (24 women) participants (20-64 years of age) completed maximum forced expiratory flow manoeuvres and measurements were performed using the following devices: MasterScreen, SensorMedics, Oxycon Pro and SpiroUSB. The order of the instruments tested was randomized and blinded for both the participants and the technicians. Re-testing was conducted on a following day within 72 hours at the same time of the day. Results: The devices which obtained the most comparable values for all lung function variables were SensorMedics and Oxycon Pro, and MasterScreen and SpiroUSB. For FEV1, mean difference was 0.04 L (95% confidence interval; -0.05, 0.14) and 0.00 L (-0.06, 0.06), respectively. When using the criterion of FVC and FEV1 ≤ 0.150 L for acceptable repeatability, 67% of the comparisons of the measured lung function values obtained by the four devices were acceptable. Overall, Oxycon Pro obtained most frequently values of the lung function variables with highest precision as indicated by the coefficients of repeatability (CR), followed by MasterScreen, SensorMedics and SpiroUSB (e.g. min-max CR for FEV1; 0.27-0.46). Conclusion: The present study confirms that measurements obtained by the same device at different times can be compared; however, measured lung function values may differ depending on spirometers used. PMID:27583055

  9. Functional Impairment in Youth Three Years after Detention

    PubMed Central

    Abram, Karen M.; Choe, Jeanne Y.; Washburn, Jason J.; Romero, Erin G.; Teplin, Linda A.

    2009-01-01

    Purpose This article examines functional impairment across global and specific dimensions among youth 3 years after their detention. Methods Functional impairment was assessed using the Child and Adolescent Functional Assessment Scale (CAFAS) in a large, stratified, random sample of formerly detained youth (N = 1653). Results More than one-fifth of the sample were scored as having marked impairment that required, at minimum, “multiple sources of care” (CAFAS Total Score of 100 or higher); 7.0% required “intensive intervention” (CAFAS Total Score ≥140). Most of the sample had impairment; only 7.5% of the sample had “no noteworthy impairment” (CAFAS Total Score ≤10). Significantly more males were impaired than females. Among males living in the community at follow-up, African Americans and Hispanics were more likely to be impaired than non-Hispanic whites. In comparison to males living in the community, males who were incarcerated at follow-up were significantly more likely to have impaired thinking and impaired functioning at their place of residence but less likely to have substance use problems. Conclusions Three years after detention, most youth struggle in one or more life domains; more than one in five have marked impairment in functioning. These findings underscore the ongoing costs, to both youth and society, of our failure to provide effective rehabilitation to youth after detention. PMID:19465316

  10. Impaired elastin deposition in Fstl1-/- lung allograft under the renal capsule.

    PubMed

    Geng, Yan; Li, Lian; Dong, Yingying; Liu, Xue; Li, Xiao-He; Ning, Wen

    2013-01-01

    Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1) is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1(-/-) lung allografts, which is similar to that of E18.5 Fstl1(-/-) lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1(-/-) allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1(-/-) lungs and at the tips of the developing alveolar septae of D7 Fstl1(-/-) allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development. PMID:24282586

  11. Individual residual symptoms and functional impairment in patients with depression.

    PubMed

    Romera, Irene; Pérez, Víctor; Quail, Deborah; Berggren, Lovisa; Lenox-Smith, Alan; Gilaberte, Inmaculada

    2014-12-15

    The aim of treatment of depression is remission of symptoms and functioning. Although there is a relationship between remission of symptoms and remission of functioning, it is not known how individual residual symptoms are related to functioning. Here we report a post-hoc analysis of two studies which treated depressed patients with duloxetine in an open fashion for 10-12 weeks. We evaluated the association of individual residual symptoms and functional impairment in patients who remitted or partially remitted after acute treatment. Logistic regression was used to investigate residual symptoms associated with functional impairment at endpoint. Our results suggest that in partial remitters, the only residual symptom associated with a reduction in the risk of having impaired function was the resolution of painful physical symptoms (PPS). In patients who remitted, the presence of residual core mood symptoms (CMS), particularly in patients without any anxiety, predicted impaired functioning. The resolution of PPS in the presence of residual CMS was associated with less risk of impaired functioning. Our results contribute to understand better the role of specific residual symptoms on functional impairment. To achieve normal functioning, intervention on specific residual symptoms is recommended. PMID:25149132

  12. Lung cancer tissue diagnosis in poor lung function: addressing the ongoing percutaneous lung biopsy FEV1 paradox using Heimlich valve.

    PubMed

    Abdullah, R; Tavare, A N; Creamer, A; Creer, D; Vancheeswaran, R; Hare, S S

    2016-08-01

    Many centres continue to decline percutaneous lung biopsy (PLB) in patients with poor lung function (particularly FEV1 <1 L) due to the theoretically increased risk of pneumothorax. This practice limits access to novel lung cancer therapies and minimally invasive surgical techniques. Our retrospective single-centre analysis of 212 patients undergoing PLB, all performed prospectively and blinded to lung function, demonstrates that using ambulatory Heimlich valve chest drain (HVCD) to treat significant postbiopsy pneumothorax facilitates safe, diagnostic, early discharge lung biopsy irrespective of lung function with neither FEV1 <1 L nor transfer coefficient for carbon monoxide (TLCO) <40% predicted shown to be independent predictors of HVCD insertion or pneumothorax outcomes. Incorporating ambulatory HVCD into standard PLB practice thereby elegantly bridges the gap that currently exists between tissue diagnosis in patients with poor lung function and the advanced therapeutic options available for this cohort. PMID:26980011

  13. Pre-operative optimisation of lung function

    PubMed Central

    Azhar, Naheed

    2015-01-01

    The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function. PMID:26556913

  14. A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

    PubMed

    Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

    2016-03-01

    The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function. PMID:26524226

  15. The EPICure Study: Association between Hemodynamics and Lung Function at 11 Years after Extremely Preterm Birth

    PubMed Central

    Bolton, Charlotte E.; Stocks, Janet; Hennessy, Enid; Cockcroft, John R.; Fawke, Joseph; Lum, Sooky; McEniery, Carmel M.; Wilkinson, Ian B.; Marlow, Neil

    2012-01-01

    Objective To investigate the relationship between disturbed lung function and large-artery hemodynamics in school-age children born extremely preterm (EP) (at 25 completed weeks of gestation or less). Study design This was a cross-sectional study of participants from the EPICure study, now aged 11 years (n = 66), and 86 age- and sex-matched term-born classmates. Spirometry parameters (including forced expiratory volume in 1 second), blood pressure, and augmentation index (AIx, a composite of arterial stiffness and global wave reflections) were measured. Results Compared with their classmates, the EP children had significantly impaired lung function, particularly those with neonatal bronchopulmonary dysplasia. Peripheral blood pressure did not differ significantly between the 2 groups, but AIx values were on average 5% higher (95% CI, 2%-8%) in the preterm infants, remaining significant after adjustment for potential confounders. Neonatal bronchopulmonary dysplasia status was not related to AIx. Lung function and maternal smoking were independently associated with AIx; AIx increased by 2.7% per z-score reduction in baseline forced expiratory volume in 1 second and by 4.9% in those whose mothers smoked during pregnancy. Conclusion The independent association between impaired lung function and cardiovascular physiology in early adolescence implies higher cardiovascular risk for children born EP, and suggests that prevention of chronic neonatal lung disease may be a priority in reducing later cardiovascular risk in preterm infants. PMID:22575246

  16. Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging.

    PubMed

    Suga, Kazuyoshi; Ogasawara, Nobuhiko; Okada, Munemasa; Tsukuda, Toshinobu; Matsunaga, Naofumi; Miyazaki, Mitsue

    2002-06-01

    A noncontrast electrocardiography (ECG)-gated, fast-spin-echo magnetic resonance imaging was applied to noninvasively define perfusion impairments in pulmonary embolic and airway obstruction dog models. Two-phase ECG-gated lung images of the minimal lung signal intensity during systole and maximal signal intensity during diastole were acquired by using optimized R-wave triggering delay times in seven dogs anesthetized with pentobarbital sodium before, soon after, and 2 mo after embolization with enbucrilate and in another eight dogs before and after bronchial occlusion with balloon catheters, in combination with a gadolinium diethylenetriaminepentaacetic acid-enhanced dynamic study. An ECG-gated subtraction image between the two-phase lung images provided a uniform but gravity-dependent perfusion map in normal lungs. Furthermore, it defined all 13 variable-size perfusion deficits associated with pulmonary embolism and the dynamically decreased perfusion with time after bronchial occlusion in all the airway obstruction models. These results were consistent with contrast-enhanced pulmonary arterial perfusion phase images. This noncontrast imaging could be equivalent to a contrast-enhanced dynamic study in the definition of regionally impaired pulmonary arterial perfusion in pulmonary embolism and airway obstruction. PMID:12015358

  17. Adenosine A2A Agonist Improves Lung Function During Ex-vivo Lung Perfusion

    PubMed Central

    Emaminia, Abbas; LaPar, Damien J.; Zhao, Yunge; Steidle, John F.; Harris, David A.; Linden, Joel; Kron, Irving L.; Lau, Christine L.

    2012-01-01

    Background Ex-vivo lung perfusion (EVLP) is a novel technique to assess, and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against lung ischemia-reperfusion injury through its A2A receptor. We hypothesized that combining EVLP with adenosine A2A receptor agonist treatment would enhance lung functional quality and increase donor lung usage. Methods Eight bilateral pig lungs were harvested and flushed with cold Perfadex. After 14 hours storage at 4°C, EVLP was performed for 5 hours on two explanted lung groups: 1) Control group lungs (n=4), were perfused with Steen Solution and Dimethyl sulfoxide (DMSO), and 2) treated group lungs (n=4) received 10μM CGS21680, a selective A2A receptor agonist, in a Steen Solution-primed circuit. Lung histology, tissue cytokines, gas analysis and pulmonary function were compared between groups. Results Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 vs. 5.2, p<0.03) and confirmed by histology. In addition, treated lung demonstrated significantly lower levels of interferon gamma (45.1 vs. 88.5, p<0.05). Other measured tissue cytokines (interleukin (IL) 1 beta, IL-6, and IL-8) were lower in treatment group, but values failed to reach statistical significance. Oxygenation index was improved in the treated group (1.5 vs. 2.3, p<0.01) as well as mean airway pressure (10.3 vs. 13 p<0.009). Conclusions EVLP is a novel and efficient way to assess and optimize lung function and oxygen exchange within donor lungs, and the use of adenosine A2A agonist potentiates its potential. EVLP with the concomitant administration of A2A agonist may enhance donor lung quality and could increase the donor lung pool for transplantation. PMID:22051279

  18. Lymphatic function is required prenatally for lung inflation at birth.

    PubMed

    Jakus, Zoltán; Gleghorn, Jason P; Enis, David R; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R; Yang, Yiqing; Hess, Paul R; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H; Nelson, Celeste M; Kahn, Mark L

    2014-05-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  19. Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer’s Disease

    PubMed Central

    Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J.; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

    2015-01-01

    Abstract Background: The temporal relationship of cognitive deficit and functional impairment in Alzheimer’s disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. Objective: To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Methods: Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. Results: In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Conclusions: Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process. PMID:26402769

  20. Profusion of opacities in simple coal workers’ pneumoconiosis is associated with reduced lung function

    PubMed Central

    Blackley, David J.; Laney, A. Scott; Halldin, Cara N.; Cohen, Robert A.

    2015-01-01

    Background A large body of evidence demonstrates dose-response relationships of cumulative coal mine dust exposure with lung function impairment and with small opacity profusion. However, medical literature generally holds that simple coal workers’ pneumoconiosis (CWP) is not associated with lung function impairment. This study examines the relationship between small opacity profusion and lung function in U.S. underground coal miners with simple CWP. Methods Miners were examined during 2005–2013 as part of the Enhanced Coal Workers’ Health Surveillance Program. Work histories were obtained, and chest radiographs and spirometry were administered. For those with multiple Program encounters, the most recent visit was used. Lung parenchymal abnormalities consistent with CWP were classified according to International Labour Organization guidelines, and reference values for FEV1 and FVC were calculated using reference equations derived from the 3rd National Health and Nutrition Examination Survey. Differences in lung function were evaluated by opacity profusion, and regression models were fit to characterize associations between profusion and lung function. Results A total of 8,230 miners were eligible for analysis; 269 had category 1 or 2 simple CWP. Decrements in FEV1 percent predicted were nearly consistent across profusion subcategories. Clear decrements in FVC percent predicted and FEV1/FVC were also observed, although these were less consistent. Controlling for smoking status, BMI, and mining tenure, each one-unit subcategory increase in profusion was associated with decreases of 1.5% (95% CI 1.0% to 1.9%), 1.0% (95% CI 0.6% to 1.3%), and 0.6% (95% CI 0.4% to 0.8%) in FEV1 percent predicted, FVC percent predicted, and FEV1/FVC, respectively. Conclusions We observed progressively lower lung function across the range of small opacity profusion. These findings address a longstanding question in occupational medicine, and point to the importance of medical

  1. Forced expiratory flows' contribution to lung function interpretation in schoolchildren.

    PubMed

    Boutin, Bernard; Koskas, Marc; Guillo, Houda; Maingot, Lucia; La Rocca, Marie-Claude; Boulé, Michèle; Just, Jocelyne; Momas, Isabelle; Corinne, Alberti; Beydon, Nicole

    2015-01-01

    Forced expiratory flow (FEF) at low lung volumes are supposed to be better at detecting lung-function impairment in asthmatic children than a forced volume. The aim of this study was to examine whether FEF results could modify the interpretation of baseline and post-bronchodilator spirometry in asthmatic schoolchildren in whom forced expiratory volumes are within the normal range. Spirometry, with post-bronchodilator vital capacity within 10% of that of baseline in healthy and asthmatic children, was recorded prospectively. We defined abnormal baseline values expressed as z-scores <-1.645, forced expiratory volume in 1 s (FEV1) reversibility as a baseline increase >12%, FEF reversibility as an increase larger than the 2.5th percentile of post-bronchodilator changes in healthy children. Among 66 healthy and 50 asthmatic schoolchildren, only two (1.7%) children with normal vital capacity and no airways obstruction had abnormal baseline forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). After bronchodilation, among the 45 asthmatic children without FEV1 reversibility, 5 (11.1%) had an FEF25-75% increase that exceeded the reference interval. Isolated abnormal baseline values or significant post-bronchodilator changes in FEF are rare situations in asthmatic schoolchildren with good spirometry quality. PMID:25186269

  2. Impairment of Caloric Function after Cochlear Implantation

    ERIC Educational Resources Information Center

    Kuang, Heide; Haversat, Heather H.; Michaelides, Elias M.

    2015-01-01

    Purpose: This article seeks to review current literature on caloric function following cochlear implantation while analyzing any correlations of caloric function changes with vestibular symptoms. Method: This article is a systematic review of evidence-based literature. English language articles published between 1980 and 2014 that presented some…

  3. Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs.

    PubMed

    Doerr, Clinton H; Gajic, Ognjen; Berrios, Jorge C; Caples, Sean; Abdel, Matthew; Lymp, James F; Hubmayr, Rolf D

    2005-06-15

    The objective of this study was to assess the effects of hypercapnic acidosis on lung cell injury and repair by confocal microscopy in a model of ventilator-induced lung injury. Three groups of normocapnic, hypocapnic, and hypercapnic rat lungs were perfused ex vivo, either during or after injurious ventilation, with a solution containing the membrane-impermeant label propidium iodide. In lungs labeled during injurious ventilation, propidium iodide fluorescence identifies all cells with plasma membrane wounds, both permanent and transient, whereas in lungs labeled after injurious ventilation propidium iodide fluorescence identifies only cells with permanent plasma membrane wounds. Hypercapnia minimized the adverse effects of high-volume ventilation on vascular barrier function, whereas hypocapnia had the opposite effect. Despite CO2-dependent differences in lung mechanics and edema the number of injured subpleural cells per alveolus was similar in the three groups (0.48 +/- 0.34 versus 0.51 +/- 0.19 versus 0.43 +/- 0.20 for hypocapnia, normocapnia, and hypercapnia, respectively). However, compared with normocapnia the probability of wound repair was significantly reduced in hypercapnic lungs (63 versus 38%; p < 0.02). This finding was subsequently confirmed in alveolar epithelial cell scratch models. The potential relevance of these observations for lung inflammation and remodeling after mechanical injury is discussed. PMID:15695495

  4. Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice

    PubMed Central

    Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2012-01-01

    Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471

  5. Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990

    PubMed Central

    Wu, J; Kreis, I; Griffiths, D; Darling, C

    2002-01-01

    Aims: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. Methods: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. Results: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV1 of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. Conclusions: Exposure to coke oven emissions was found to be associated with lower FEV1 and FVC. Effects of work exposure on lung function are similar to those found in other studies. PMID:12468747

  6. Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group.

    PubMed

    Herve, P; Silbert, D; Cerrina, J; Simonneau, G; Dartevelle, P

    1993-01-01

    The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation. PMID:8380268

  7. Impaired physical function following pediatric LT.

    PubMed

    Feldman, Amy G; Neighbors, Katie; Mukherjee, Shubhra; Rak, Melanie; Varni, James W; Alonso, Estella M

    2016-04-01

    The purpose of this article is to investigate the spectrum of physical function of pediatric liver transplantation (LT) recipients 12-24 months after LT. Review data were collected through the functional outcomes group, an ancillary study of the Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12-24 months. Children ≥ 8 years and parents completed the Pediatric Quality of Life Inventory™ 4.0 generic core scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n = 1658) and between survivors with optimal versus nonoptimal health. A total of 263 patients were included. Median age at transplant and survey was 4.8 years (interquartile range [IQR], 1.3-11.4 years) and 5.9 years (IQR, 2.6-13.1 years), respectively. The mean physical functioning score on child and parent reports were 81.2 ± 17.3 and 77.1 ± 23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (P < 0.001); 32.9% of patients and 35.0% of parents reported a physical function score <75, which is > 1 standard deviation below the mean of a healthy population. Physical functioning scores were significantly higher in survivors with optimal health than those with nonoptimal health (P < 0.01). There was a significant relationship between emotional functioning and physical functioning scores for LT recipients (r = 0.69; P < 0.001). In multivariate analysis, primary disease, height z score < -1.64 at longterm follow-up (LTF) visit,  > 4 days of hospitalization since LTF visit, and not being listed as status 1 were predictors of poor physical function. In conclusion, pediatric LT recipients 1-2 years after LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and

  8. Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis.

    PubMed

    Fernandez, Isis E; Amarie, Oana V; Mutze, Kathrin; Königshoff, Melanie; Yildirim, Ali Önder; Eickelberg, Oliver

    2016-05-15

    To date, phenotyping and disease course prediction in idiopathic pulmonary fibrosis (IPF) primarily relies on lung function measures. Blood biomarkers were recently proposed for diagnostic and outcome prediction in IPF, yet their correlation with lung function and histology remains unclear. Here, we comprehensively assessed biomarkers in liquid biopsies and correlated their abundance with lung function and histology during the onset, progression, and resolution of lung fibrosis, with the aim to more precisely evaluate disease progression in the preclinical model of bleomycin-induced pulmonary fibrosis in vivo. Importantly, the strongest correlation of lung function with histological extent of fibrosis was observed at day 14, whereas lung function was unchanged at days 28 and 56, even when histological assessment showed marked fibrotic lesions. Although matrix metalloproteinase-7 (MMP-7), MMP-9, and PAI-1 were significantly elevated in broncheoalveolar lavage of fibrotic mice, only soluble ICAM-1 (sICAM-1) was elevated in the peripheral blood of fibrotic mice and was strongly correlated with the extent of fibrosis. Importantly, tissue-bound ICAM-1 was also elevated in lung homogenates, with prominent staining in hyperplastic type II alveolar epithelial and endothelial cells. In summary, we show that lung function decline is not a prerequisite for histologically evident fibrosis, particularly during the onset or resolution thereof. Plasma levels of sICAM-1 strongly correlate with the extent of lung fibrosis, and may thus be considered for the assessment of intraindividual therapeutic studies in preclinical studies of pulmonary fibrosis. PMID:26993522

  9. Hypothermic lung preservation functions, six or more years later.

    PubMed Central

    Garzon, A A; Goldstein, S; Okadigwe, C I; Paley, N B; Minkowitz, S

    1977-01-01

    The functions of each lung were measured 41 and 79 months following hypothermic twenty-four four lung preservation and autotransplantation in six and four dogs respectively. Functional results were compared with long-term autotransplanted canine lungs. Compliance, total lung capacity, functional reserve capacity and ventilation of preserved lungs were similar to autotransplanted lungs, and only slightly decreased as compared with normal animals. There was no statistically significant difference between the pulmonary diffusion capacity and oxygen uptake of the preserved and autotransplanted lungs group and autotransplants alone. However, in both groups, diffusion capacity and oxygen uptake were decreased as compared with intact animals. Pulmonary hypertension was found on occlusion of the contralateral lung's artery: it was due to increased pulmonary vascular resistance. No gross narrowing of the pulmonary artery or venous anastomosis was found that could explain the increased resistance. Diffuse emphysema of various degrees was observed in all animals. This study seems to indicate that hypothermic preservation of the lung does not affect significantly the long-term functional ability of the organ, and probably will have practical value in future clinical lung transplantation. Images Fig. 1. PMID:341822

  10. Triadin Deletion Induces Impaired Skeletal Muscle Function*

    PubMed Central

    Oddoux, Sarah; Brocard, Julie; Schweitzer, Annie; Szentesi, Peter; Giannesini, Benoit; Brocard, Jacques; Fauré, Julien; Pernet-Gallay, Karine; Bendahan, David; Lunardi, Joël; Csernoch, Laszlo; Marty, Isabelle

    2009-01-01

    Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and some having still unknown functions. To obtain clues on triadin functions, we engineered a triadin knock-out mouse line and characterized the physiological effect of triadin ablation on skeletal muscle function. These mice presented a reduced muscle strength, which seemed not to alter their survival and has been characterized in the present work. We first checked in these mice the expression level of the different proteins involved in calcium homeostasis and observed in fast muscles an increase in expression of dihydropyridine receptor, with a large reduction in calsequestrin expression. Electron microscopy analysis of KO muscles morphology demonstrated the presence of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum terminal cisternae volume. Using calcium imaging on cultured myotubes, we observed a reduction in the total amount of calcium stored in the sarcoplasmic reticulum. Physiological studies have been performed to evaluate the influence of triadin deletion on skeletal muscle function. Muscle strength has been measured both on the whole animal model, using hang test or electrical stimulation combined with NMR analysis and strength measurement, or on isolated muscle using electrical stimulation. All the results obtained demonstrate an important reduction in muscle strength, indicating that triadin plays an essential role in skeletal muscle function and in skeletal muscle structure. These results indicate that triadin alteration leads to the development of a myopathy, which could be studied using this new animal model. PMID:19843516

  11. Functional Impairment and Occupational Outcome in Adults with ADHD

    ERIC Educational Resources Information Center

    Gjervan, Bjorn; Torgersen, Terje; Nordahl, Hans M.; Rasmussen, Kirsten

    2012-01-01

    Objective: ADHD is associated with poor functional outcomes. The objectives were to investigate the prevalence of functional impairment and occupational status in a clinically referred sample of adults with ADHD and explore factors predicting occupational outcome. Method: A sample of 149 adults with a confirmed diagnosis of ADHD participated in…

  12. Relationship of structural to functional impairment during alveolar-capillary membrane development.

    PubMed

    Ahlfeld, Shawn K; Gao, Yong; Conway, Simon J; Tepper, Robert S

    2015-04-01

    Bronchopulmonary dysplasia is a chronic lung disease of extreme preterm infants and results in impaired gas exchange. Although bronchopulmonary dysplasia is characterized histologically by alveolar-capillary simplification in animal models, it is clinically defined by impaired gas diffusion. With the use of a developmentally relevant model, we correlated alveolar-capillary structural simplification with reduced functional gas exchange as measured by the diffusing factor for carbon monoxide (DFCO). Neonatal mouse pups were exposed to >90% hyperoxia or room air during postnatal days 0 to 7, and then all pups were returned to room air from days 7 to 56. At day 56, DFCO was measured as the ratio of carbon monoxide uptake to neon dilution, and lungs were fixed for histologic assessment of alveolar-capillary development. Neonatal hyperoxia exposure inhibited alveolar-capillary septal development as evidenced by significantly increased mean linear intercept, increased airspace-to-septal ratio, decreased nodal density, and decreased pulmonary microvasculature. Importantly, alveolar-capillary structural deficits in hyperoxia-exposed pups were accompanied by a significant 28% decrease in DFCO (0.555 versus 0.400; P < 0.0001). In addition, DFCO was highly and significantly correlated with structural measures of reduced alveolar-capillary growth. Simplification of alveolar-capillary structure is highly correlated with impaired gas exchange function. Current mechanistic and therapeutic animal models of inhibited alveolar development may benefit from application of DFCO as an alternative physiologic indicator of alveolar-capillary development. PMID:25661110

  13. Phonatory Function of Neurologically Impaired Patients.

    ERIC Educational Resources Information Center

    Zwirner, Petra; And Others

    1991-01-01

    This investigation compared five parameters of phonatory function in an examination of the use of acoustic measures in differential diagnosis in 39 subjects in 3 neuropathological groups (Parkinson, Huntington, cerebellar ataxia) and a normal control group. Results indicated higher variability in perturbation in all the neuropathological groups.…

  14. LUNG FUNCTION IN SCHOOL CHILDREN: 1971-1972 CHATTANOOGA STUDY

    EPA Science Inventory

    Previous studies of lung function in children have indicated that decreases in lung function are associated with higher air pollution exposures. For this reason, three quarter second timed forced expiratory volume was chosen as one of the health indicators in the Environmental Pr...

  15. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function.

    PubMed

    Paganin, Patrizia; Fiscarelli, Ersilia Vita; Tuccio, Vanessa; Chiancianesi, Manuela; Bacci, Giovanni; Morelli, Patrizia; Dolce, Daniela; Dalmastri, Claudia; De Alessandri, Alessandra; Lucidi, Vincenzina; Taccetti, Giovanni; Mengoni, Alessio; Bevivino, Annamaria

    2015-01-01

    Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the

  16. Pharmacokinetics of oral cefatrizine in patients with impaired renal function.

    PubMed

    Couet, W; Fauvel, J P; Laville, M; Pozet, N; Fourtillan, J B

    1991-06-01

    The pharmacokinetics of cefatrizine was studied in 15 patients with various degrees of renal impairment, after single oral administration of 500 mg. Cefatrizine elimination was reduced in parallel to renal function, as indicated by the significant correlations between apparent clearance (Cl/F) and creatinine clearance (Clcr), and between renal clearance (Clr) and creatinine clearance (Clcr). In patients with totally impaired renal function, the residual clearance (Cl/F) was 63 ml.min-1 per 1.73 m2. Comparisons with previously published data indicate that the apparent volume of distribution (V/F) of cefatrizine was lower in patients with impaired renal function than in young healthy volunteers, leading to increased peak concentrations (Cmax), but there was no relationship between V/F and Clcr. In patients with totally impaired renal function, the upper limit of cefatrizine elimination half-life was estimated to 5.5 h. The clinical significance of pharmacokinetic modifications observed in renal disease patients may only be realized through integration of pharmacodynamic characteristics of cefatrizine. The observed increase in Cmax and the lengthening of t1/2 could suggest a reduction of dosing frequency in patients with severe renal impairment. PMID:1869342

  17. Evaluation of effect of impaired renal function on lamivudine pharmacokinetics

    PubMed Central

    Bouazza, Naïm; Tréluyer, Jean-Marc; Ghosn, Jade; Hirt, Déborah; Benaboud, Sihem; Foissac, Frantz; Viard, Jean-Paul; Urien, Saik

    2014-01-01

    Aims This study aimed to describe lamivudine pharmacokinetics in patients with impaired renal function and to evaluate the consistency of current dosing recommendations. Methods A total of 244 patients, ranging in age from 18 to 79 years (median 40 years) and in bodyweight from 38 to 117 kg (median 71 kg), with 344 lamivudine plasma concentrations, were analysed using a population pharmacokinetic analysis. Serum creatinine clearance (CLCR) was calculated using the Cockcroft–Gault formula; 177 patients had normal renal function (CLCR > 90 ml min−1), 50 patients had mild renal impairment (CLCR = 60–90 ml min−1), 20 patients had moderate renal impairment (CLCR = 30–60 ml min−1), and five patients had severe renal impairment (CLCR < 30 ml min−1). Results A two-compartment model adequately described the data. Typical population estimates (percentage interindividual variability) of the apparent clearance (CL/F), central (Vc/F) and peripheral volumes of distribution (Vp/F), intercompartmental clearance (Q/F) and absorption rate constant (Ka) were 29.7 l h−1 (32%), 68.2 l, 114 l, 10.1 l h−1 (85%) and 1 h−1, respectively. Clearance increased significantly and gradually with CLCR. Our simulations showed that a dose of 300 mg day−1 in patients with mild renal impairment could overexpose them. A dose of 200 mg day−1 maintained an exposure close to that of adults with normal renal function. However, the current US Food and Drug Administration recommendations for lamivudine in other categories of patients (from severe to moderate renal impairment) provided optimal exposures. Conclusions Lamivudine elimination clearance is related to renal function. To provide optimal exposure, patients with mild renal impairment should receive 200 mg day−1 instead of 300 mg day−1. PMID:24750102

  18. Fancb deficiency impairs hematopoietic stem cell function

    PubMed Central

    Du, Wei; Amarachintha, Surya; Erden, Ozlem; Wilson, Andrew; Meetei, Amom Ruhikanta; Andreassen, Paul R.; Namekawa, Satoshi H.; Pang, Qishen

    2015-01-01

    Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, variable congenital malformations and a predisposition to malignancies. FANCB (also known as FAAP95), is the only X-linked FA gene discovered thus far. In the present study, we investigated hematopoiesis in adult Fancb deficient (Fancb−/y) mice and found that Fancb−/y mice have decreased hematopoietic stem cell (HSC) quiescence accompanied by reduced progenitor activity in vitro and reduced repopulating capacity in vivo. Like other FA mouse models previously reported, the hematopoietic system of Fancb−/y mice is hypersensitive to DNA cross-linking agent mitomycin C (MMC), which induces bone marrow failure in Fancb−/y mice. Furthermore, Fancb−/y BM exhibits slower recovery kinetics and less tolerance to myelotoxic stress induced by 5-fluorouracil than wild-type littermates. RNA-seq analysis reveals altered expression of genes involved in HSC function and cell cycle regulation in Fancb−/y HSC and progenitor cells. Thus, this Fancb−/y mouse model provides a novel approach for studying the critical role of the FA pathway not only in germ cell development but also in the maintenance of HSC function. PMID:26658157

  19. Topoisomerase 1 inhibition reversibly impairs synaptic function

    PubMed Central

    Mabb, Angela M.; Kullmann, Paul H. M.; Twomey, Margaret A.; Miriyala, Jayalakshmi; Philpot, Benjamin D.; Zylka, Mark J.

    2014-01-01

    Topotecan is a topoisomerase 1 (TOP1) inhibitor that is used to treat various forms of cancer. We recently found that topotecan reduces the expression of multiple long genes, including many neuronal genes linked to synapses and autism. However, whether topotecan alters synaptic protein levels and synapse function is currently unknown. Here we report that in primary cortical neurons, topotecan depleted synaptic proteins that are encoded by extremely long genes, including Neurexin-1, Neuroligin-1, Cntnap2, and GABAAβ3. Topotecan also suppressed spontaneous network activity without affecting resting membrane potential, action potential threshold, or neuron health. Topotecan strongly suppressed inhibitory neurotransmission via pre- and postsynaptic mechanisms and reduced excitatory neurotransmission. The effects on synaptic protein levels and inhibitory neurotransmission were fully reversible upon drug washout. Collectively, our findings suggest that TOP1 controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission. PMID:25404338

  20. Metabolic Functions of the Lung, Disorders and Associated Pathologies

    PubMed Central

    Alvarado, Alcibey; Arce, Isabel

    2016-01-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth’s atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  1. Association between the Type of Workplace and Lung Function in Copper Miners

    PubMed Central

    Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

    2016-01-01

    The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

  2. Neural origins of psychosocial functioning impairments in major depression.

    PubMed

    Pulcu, Erdem; Elliott, Rebecca

    2015-09-01

    Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return. PMID:26360902

  3. Hypercholesterolemia Impaired Sperm Functionality in Rabbits

    PubMed Central

    Monclus, Maria A.; Cabrillana, Maria E.; Clementi, Marisa A.; Espínola, Leandro S.; Cid Barría, Jose L.; Vincenti, Amanda E.; Santi, Analia G.; Fornés, Miguel W.

    2010-01-01

    Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events. PMID:20976152

  4. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

    PubMed Central

    2013-01-01

    Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

  5. Executive Functioning in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Henry, Lucy A.; Messer, David J.; Nash, Gilly

    2012-01-01

    Background: A limited range of evidence suggests that children with specific language impairment (SLI) have difficulties with higher order thinking and reasoning skills (executive functioning, EF). This study involved a comprehensive investigation of EF in this population taking into account the contributions of age, nonverbal IQ and verbal…

  6. Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

    SciTech Connect

    Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

    2009-07-01

    Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

  7. Altered lung function at mid-adulthood in mice following neonatal exposure to hyperoxia.

    PubMed

    Sozo, Foula; Horvat, Jay C; Essilfie, Ama-Tawiah; O'Reilly, Megan; Hansbro, Philip M; Harding, Richard

    2015-11-01

    Infants born very preterm are usually exposed to high oxygen concentrations but this may impair lung function in survivors in later life. However, the precise changes involved are poorly understood. We determined how neonatal hyperoxia alters lung function at mid-adulthood in mice. Neonatal C57BL/6J mice inhaled 65% oxygen (HE group) from birth for 7 days. They then breathed room air until 11 months of age (P11mo); these mice experienced growth restriction. Controls breathed only room air. To exclude the effects of growth restriction, a group of dams was rotated between hyperoxia and normoxia during the exposure period (HE+DR group). Lung function was measured at P11mo. HE mice had increased inspiratory capacity, work of breathing and tissue damping. HE+DR mice had further increases in inspiratory capacity and work of breathing, and reduced FEV100/FVC. Total lung capacity was increased in HE+DR males. HE males had elevated responses to methacholine. Neonatal hyperoxia alters lung function at mid-adulthood, especially in males. PMID:26197245

  8. Correlation of Apical Fluid-Regulating Channel Proteins with Lung Function in Human COPD Lungs

    PubMed Central

    Zhao, Meimi; Liu, Shan-Lu; Huang, Yao; Idell, Steven; Li, Xiumin; Ji, Hong-Long

    2014-01-01

    Links between epithelial ion channels and chronic obstructive pulmonary diseases (COPD) are emerging through animal model and in vitro studies. However, clinical correlations between fluid-regulating channel proteins and lung function in COPD remain to be elucidated. To quantitatively measure epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporin 5 (AQP5) proteins in human COPD lungs and to analyze the correlation with declining lung function, quantitative western blots were used. Spearman tests were performed to identify correlations between channel proteins and lung function. The expression of α and β ENaC subunits was augmented and inversely associated with lung function. In contrast, both total and alveolar type I (ATI) and II (ATII)-specific CFTR proteins were reduced. The expression level of CFTR proteins was associated with FEV1 positively. Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively. Furthermore, these channel proteins were significantly associated with severity of disease. Our study demonstrates that expression of ENaC, AQP5, and CFTR proteins in human COPD lungs is quantitatively associated with lung function and severity of COPD. These apically located fluid-regulating channels may thereby serve as biomarkers and potent druggable targets of COPD. PMID:25329998

  9. PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

    PubMed Central

    Cukic, Vesna

    2012-01-01

    Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

  10. Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

    PubMed

    Das, Banibrata

    2016-07-01

    Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers. PMID:26176596

  11. Mild carbon monoxide poisoning impairs left ventricular diastolic function

    PubMed Central

    Çiftçi, Özgür; Günday, Murat; Çalışkan, Mustafa; Güllü, Hakan; Doğan, Rafi; Güven, Aytekin; Müderrisoğlu, Haldun

    2013-01-01

    Rationale: Carbon monoxide (CO) poisoning is associated with direct cardiovascular toxicity. In mild CO poisoning in which cardiovascular life support is not required, the effects of CO on left and right ventricular functions are unknown in patients without cardiac failure. Objectives: Echocardiography was used to determine whether or not mild CO poisoning impairs ventricular function. Twenty otherwise healthy patients with CO poisoning and 20 age- and gender-matched controls were studied. Echocardiographic examinations were performed at the time of admission and 1 week after poisoning. Results: The impairment observed in the left and right ventricular diastolic function at the time of admission was greater than the impairment 1 week after poisoning. Mild CO poisoning did not have a significant effect on systolic function. Carboxyhemoglobin levels were positively correlated with left ventricular diastolic dysfunction, whereas the levels were not correlated with right ventricular diastolic function. Conclusions: In CO intoxication, the development of left and right ventricular diastolic dysfunction precedes systolic abnormality. Patients with mild CO poisoning do not manifest cardiovascular symptoms; however, it should be borne in mind that most of these patients have myocardial involvement. PMID:24082611

  12. Exercise testing in severe emphysema: association with quality of life and lung function.

    PubMed

    Brown, Cynthia D; Benditt, Joshua O; Sciurba, Frank C; Lee, Shing M; Criner, Gerard J; Mosenifar, Zab; Shade, David M; Slivka, William A; Wise, Robert A

    2008-04-01

    Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV(1) of 26.9 +/- 7.1 % predicted. Predicted values for 6MWT and CPX were calculated from reference equations. Correlation coefficients and multivariable regression models were used to determine the association between lung function, quality of life (QOL) scores, and exercise measures. The two forms of exercise testing were correlated with each other (r = 0.57, p < 0.0001). However, the impairment of performance on CPX was greater than on the 6MWT (27.6 +/- 16.8 vs. 67.9 +/- 18.9 % predicted). Both exercise tests had similar correlation with measures of QOL, but maximum exercise capacity was better correlated with lung function measures than 6-minute walk distance. After adjustment, 6MWD had a slightly greater association with total SGRQ score than maximal exercise (effect size 0.37 +/- 0.04 vs. 0.25 +/- 0.03 %predicted/unit). Despite advanced emphysema, patients are able to maintain 6MWD to a greater degree than maximum exercise capacity. Moreover, the 6MWT may be a better test of functional capacity given its greater association with QOL measures whereas CPX is a better test of physiologic impairment. PMID:18415810

  13. Brief Exposure to Secondhand Smoke Reversibly Impairs Endothelial Vasodilatory Function

    PubMed Central

    2014-01-01

    Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function. PMID:24302638

  14. Impairment of phagocytic functions of alveolar macrophages by hydrogen peroxide

    SciTech Connect

    Oosting, R.S.; van Bree, L.; van Iwaarden, J.F.; van Golde, L.M.; Verhoef, J. )

    1990-08-01

    Hydrogen peroxide (H2O2) inhibited phagocytosis and superoxide anion production by rat alveolar macrophages. The inhibition was irreversible and concentration and exposure time dependent. The potential relationship between H2O2-induced biochemical perturbations and impaired alveolar macrophage phagocytic functions was investigated. Alveolar macrophage viability and Fc receptor binding capacity were not affected by H2O2. There was probably no correlation between a H2O2-induced rise in cytosolic (Ca2+) ((Ca2+)i) and the impairment of phagocytosis by alveolar macrophages, as was suggested by the following findings. First, the H2O2-induced rise in (Ca2+)i could be inhibited by chelation of extracellular Ca2+, whereas the H2O2-induced impairment of phagocytosis could not. Second, the H2O2-induced rise in (Ca2+)i was reversible, whereas the impairment of phagocytosis was not. And finally, a rise in (Ca2+)i by incubation of alveolar macrophages with the calcium ionophore A23187 did not affect phagocytosis. Various experiments suggested that ATP depletion may play an important role in the H2O2 toxicity for alveolar macrophages. Comparable concentrations of H2O2 caused an irreversible decrease both in cellular ATP and in phagocytosis and superoxide production by alveolar macrophages. In addition, time course of ATP depletion and induction of impaired alveolar macrophage function were similar. In view of the fact that the strong oxidant H2O2 may react with a large variety of biological substances, possible other toxic lesions may not be excluded as underlying mechanism for H2O2-induced inhibition of phagocytic functions of alveolar macrophages.

  15. Insulin Resistance and Impaired Mitochondrial Function in Obese Adolescent Girls

    PubMed Central

    Bredella, Miriam A.; Thakur, Hena; Torriani, Martin; Misra, Madhusmita

    2014-01-01

    Abstract Background: Mitochondrial dysfunction plays a role in the development of muscle insulin resistance (IR) and the accumulation of intramyocellular lipid (IMCL) in skeletal muscle that can, in turn, interfere with insulin signaling. The purpose of this study was to assess mitochondrial function (MF) and IMCL in obese adolescent girls with and without IR to determine whether: (1) Girls with IR have impaired MF, and (2) impaired MF in girls with IR is related to higher IMCL. Methods: We examined 22 obese girls aged 13–21 years old for IR [defined as a homeostasis model assessment of insulin resistance (HOMA-IR) value >4. Phosphorus magnetic resonance spectroscopy (31P-MRS) and proton magnetic resonance spectroscopy (1H-MRS), respectively, were used to determine MF and IMCL of the soleus muscle along with magnetic resonance imaging (MRI) measures of visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) in girls with HOMA-IR >4 (insulin-resistant group) versus HOMA-IR ≤4 (insulin-sensitive group). Serum lipids and waist-to-hip ratio (W/H) were also measured. Results: Girls with IR (n=8) did not differ from the insulin-sensitive group (n=14) for age, bone age, weight, VAT, SAT, TAT, or IMCL. However, the insulin-resistant group had higher W/H. Additionally the insulin-resistance group had a lower log rate of postexercise phosphocreatine (PCr) recovery (ViPCr) and a higher log PCr recovery constant (tau), indicative of impaired MF. Conclusions: Obese girls with increased IR have impaired mitochondrial function. This association is not mediated by alterations in IMCL or adipose tissue. Further studies are necessary to determine whether there is a causal relation between impaired mitochondrial function and IR in obesity and mediators of such a relationship. PMID:24251951

  16. Impaired Pulmonary Defense Against Pseudomonas aeruginosa in VEGF Gene Inactivated Mouse Lung

    PubMed Central

    Breen, Ellen C.; Malloy, Jaret L.; Tang, Kechun; Xia, Feng; Fu, Zhenxing; Hancock, Robert E. W.; Overhage, Joerg; Wagner, Peter D.; Spragg, Roger G.

    2012-01-01

    Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung-targeted VEGF gene inactivation, and alterations in VEGF-dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF-deficient lungs increased PAO1 levels and pro-inflammatory cytokines, TNFα and IL-6, were detected 24 hours after bacterial instillation compared to control lungs. In vivo lung-targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA and SP-D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D. TPA-induced DSPC secretion and apoptosis were elevated in VEGF-deficient type II cells. These results suggest a potential protective role for type II cell-expressed VEGF against bacterial initiated infection. PMID:22718316

  17. Hyperpolarized Xenon-129 Magnetic Resonance Imaging of Functional Lung Microstructure

    NASA Astrophysics Data System (ADS)

    Dregely, Isabel

    Hyperpolarized 129Xe (HXe) is a non-invasive contrast agent for lung magnetic resonance imaging (MRI), which upon inhalation follows the functional pathway of oxygen in the lung by dissolving into lung tissue structures and entering the blood stream. HXe MRI therefore provides unique opportunities for functional lung imaging of gas exchange which occurs from alveolar air spaces across the air-blood boundary into parenchymal tissue. However challenges in acquisition speed and signal-to-noise ratio have limited the development of a HXe imaging biomarker to diagnose lung disease. This thesis addresses these challenges by introducing parallel imaging to HXe MRI. Parallel imaging requires dedicated hardware. This work describes design, implementation, and characterization of a 32-channel phased-array chest receive coil with an integrated asymmetric birdcage transmit coil tuned to the HXe resonance on a 3 Tesla MRI system. Using the newly developed human chest coil, a functional HXe imaging method, multiple exchange time xenon magnetization transfer contrast (MXTC) is implemented. MXTC dynamically encodes HXe gas exchange into the image contrast. This permits two parameters to be derived regionally which are related to gas-exchange functionality by characterizing tissue-to-alveolar-volume ratio and alveolar wall thickness in the lung parenchyma. Initial results in healthy subjects demonstrate the sensitivity of MXTC by quantifying the subtle changes in lung microstructure in response to orientation and lung inflation. Our results in subjects with lung disease show that the MXTC-derived functional tissue density parameter exhibits excellent agreement with established imaging techniques. The newly developed dynamic parameter, which characterizes the alveolar wall, was elevated in subjects with lung disease, most likely indicating parenchymal inflammation. In light of these observations we believe that MXTC has potential as a biomarker for the regional quantification of 1

  18. Regional lung function and mechanics using image registration

    NASA Astrophysics Data System (ADS)

    Ding, Kai

    The main function of the respiratory system is gas exchange. Since many disease or injury conditions can cause biomechanical or material property changes that can alter lung function, there is a great interest in measuring regional lung function and mechanics. In this thesis, we present a technique that uses multiple respiratory-gated CT images of the lung acquired at different levels of inflation with both breath-hold static scans and retrospectively reconstructed 4D dynamic scans, along with non-rigid 3D image registration, to make local estimates of lung tissue function and mechanics. We validate our technique using anatomical landmarks and functional Xe-CT estimated specific ventilation. The major contributions of this thesis include: (1) developing the registration derived regional expansion estimation approach in breath-hold static scans and dynamic 4DCT scans, (2) developing a method to quantify lobar sliding from image registration derived displacement field, (3) developing a method for measurement of radiation-induced pulmonary function change following a course of radiation therapy, (4) developing and validating different ventilation measures in 4DCT. The ability of our technique to estimate regional lung mechanics and function as a surrogate of the Xe-CT ventilation imaging for the entire lung from quickly and easily obtained respiratory-gated images, is a significant contribution to functional lung imaging because of the potential increase in resolution, and large reductions in imaging time, radiation, and contrast agent exposure. Our technique may be useful to detect and follow the progression of lung disease such as COPD, may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy.

  19. Impaired renal function and bleeding in elderly treated with dabigatran.

    PubMed

    Berthelot, Emmanuelle; Lavenu-Bombled, Cecile; Orostegui-Giron, Lupe; Desconclois, Céline; Assayag, Patrick

    2014-09-01

    Advantages of dabigatran, a thrombin inhibitor, for stroke prevention in patients with atrial fibrillation are numerous. Elderly patients with impaired renal function are at high risk of bleeding. Recommendations about the renal monitoring in elderly patients are not precise enough. The hemoclot direct thrombin inhibitor (HTI) assay measures accurately the dabigatran activity. Both could help managing serious bleeding events in selected populations. Four elderly patients recently treated with appropriate doses of dabigatran were hospitalized for major bleeding. Three patients were very elderly (> 80 years) and three had impaired renal function (clearance < 50 ml/min) before treatment initiation. Serious bleeding events occurred shortly after dabigatran initiation (< 2 months). In all cases, there was a documented dabigatran plasma overdose associated with a renal function impairment concomitant with the bleeding. Why should physicians be aware of this finding?: A close follow-up of the renal function in clinically fragile elderly patient, before and during the weeks following dabigatran initiation, could help to detect the risk of major bleeding event. The HTI dosage could help managing the treatment in case of severe bleeding event. PMID:24509332

  20. Systematic review of pleural plaques and lung function

    PubMed Central

    Kerper, Laura E.; Lynch, Heather N.; Zu, Ke; Tao, Ge; Utell, Mark J.

    2015-01-01

    Abstract Context US EPA proposed a Reference Concentration for Libby amphibole asbestos based on the premise that pleural plaques are adverse and cause lung function deficits. Objective We conducted a systematic review to evaluate whether there is an association between pleural plaques and lung function and ascertain whether results were dependent on the method used to identify plaques. Methods Using the PubMed database, we identified studies that evaluated pleural plaques and lung function. We assessed each study for quality, then integrated evidence and assessed associations based on the Bradford Hill guidelines. We also compared the results of HRCT studies to those of X-ray studies. Results We identified 16 HRCT and 36 X-ray studies. We rated six HRCT and 16 X-ray studies as higher quality based on a risk-of-bias analysis. Half of the higher quality studies reported small but statistically significant mean lung function decrements associated with plaques. None of the differences were clinically significant. Many studies had limitations, such as inappropriate controls and/or insufficient adjustment for confounders. There was little consistency in the direction of effect for the most commonly reported measurements. X-ray results were more variable than HRCT results. Pleural plaques were not associated with changes in lung function over time in longitudinal studies. Conclusion The weight of evidence indicates that pleural plaques do not impact lung function. Observed associations are most likely due to unidentified abnormalities or other factors. PMID:25518994

  1. Functional Literacy for Students with Visual Impairments and Significant Cognitive Disabilities: The Perspective of Teachers of Students with Visual Impairments

    ERIC Educational Resources Information Center

    Zebehazy, Kim T.

    2014-01-01

    This study reports opinions and practices of teachers of students with visual impairments (TSVIs) in 34 states regarding functional literacy for students with visual impairments (VIs) and significant cognitive disabilities (SCDs). The survey asked TSVIs to select a definition of functional literacy, indicate agreement with a series of literacy…

  2. A Comparative Study of Lung Host Defense in Murine Obesity Models. Insights into Neutrophil Function.

    PubMed

    Ubags, Niki D J; Burg, Elianne; Antkowiak, Maryellen; Wallace, Aaron M; Dilli, Estee; Bement, Jenna; Wargo, Matthew J; Poynter, Matthew E; Wouters, Emiel F M; Suratt, Benjamin T

    2016-08-01

    We have shown that obesity-associated attenuation of murine acute lung injury is driven, in part, by blunted neutrophil chemotaxis, yet differences were noted between the two models of obesity studied. We hypothesized that obesity-associated impairment of multiple neutrophil functions contributes to increased risk for respiratory infection but that such impairments may vary between murine models of obesity. We examined the most commonly used murine obesity models (diet-induced obesity, db/db, CPE(fat/fat), and ob/ob) using a Klebsiella pneumoniae pneumonia model and LPS-induced pneumonitis. Marrow-derived neutrophils from uninjured lean and obese mice were examined for in vitro functional responses. All obesity models showed impaired clearance of K. pneumoniae, but in differing temporal patterns. Failure to contain infection in obese mice was seen in the db/db model at both 24 and 48 hours, yet this defect was only evident at 24 hours in CPE(fat/fat) and ob/ob models, and at 48 hours in diet-induced obesity. LPS-induced airspace neutrophilia was decreased in all models, and associated with blood neutropenia in the ob/ob model but with leukocytosis in the others. Obese mouse neutrophils from all models demonstrated impaired chemotaxis, whereas neutrophil granulocyte colony-stimulating factor-mediated survival, LPS-induced cytokine transcription, and mitogen-activated protein kinase and signal transducer and activator of transcription 3 activation in response to LPS and granulocyte colony-stimulating factor, respectively, were variably impaired across the four models. Obesity-associated impairment of host response to lung infection is characterized by defects in neutrophil recruitment and survival. However, critical differences exist between commonly used mouse models of obesity and may reflect variable penetrance of elements of the metabolic syndrome, as well as other factors. PMID:27128821

  3. Rapamycin inhibited the function of lung CSCs via SOX2.

    PubMed

    Xie, Li-Xia; Sun, Feng-Feng; He, Bin-Feng; Zhan, Xiao-Feng; Song, Juan; Chen, Sheng-Song; Yu, Shi-Cang; Ye, Xiao-Qun

    2016-04-01

    The presence of cancer stem cells (CSCs) is the source of occurrence, aggravation, and recurrence of lung cancer. Accordingly, targeting killing the lung CSCs has been suggested to be an effective approach for lung cancer treatment. In this study, we showed that rapamycin inhibited the mammalian target of rapamycin (mTOR) signal transduction in A549 cells and improved the sensitivity to cisplatin (DDP). The mechanisms involve inhibition of the SOX2 expression, cell proliferation, epithelial-mesenchymal transition (EMT) phenotype, and sphere formation. Interestingly, knocked down SOX2 was a similar effect with rapamycin in A549 sphere. Furthermore, we showed that ectopic expression of Sox2 in A549 cells was sufficient to render them more resistant to rapamycin treatment in vitro. These data suggested that rapamycin inhibited the function of lung CSCs via SOX2. It will be of great interest to further explore the therapeutic strategies of lung cancer. PMID:26526583

  4. Impairment of Endothelial Function by Little Cigar Secondhand Smoke

    PubMed Central

    Liu, Jiangtao; Wang, Xiaoyin; Narayan, Shilpa; Glantz, Stanton A.; Schick, Suzaynn F.; Springer, Matthew L.

    2015-01-01

    Objectives Little cigars and cigarillos are gaining in popularity as cigarette use wanes, mainly due to relaxed regulatory standards that make them cheaper, easier to buy individually, and available in a variety of flavors not allowed in cigarettes. To address whether they should be regulated as strictly as cigarettes, we investigated whether little cigar secondhand smoke (SHS) decreases vascular endothelial function like that of cigarettes. Methods We exposed rats to SHS from little cigars, cigarettes, or chamber air, for 10 minutes and measured the resulting acute impairment of arterial flow-mediated dilation (FMD). Results SHS from both little cigars and cigarettes impaired FMD. Impairment was greater after exposure to little cigar SHS than by cigarette SHS relative to pre-exposure values, although the post-exposure FMD values were not significantly different from each other. Conclusions Exposure to little cigar SHS leads to impairment of FMD that is at least equal to that resulting from similar levels of cigarette SHS. Our findings support the need to prevent even brief exposure to little cigar SHS, and support tobacco control policies that regulate little cigars as strictly as cigarettes. PMID:26753171

  5. Prenatal ethanol exposure impairs executive function in mice into adulthood

    PubMed Central

    Marquardt, Kristin; Sigdel, Rahul; Caldwell, Kevin; Brigman, Jonathan L.

    2014-01-01

    Background Despite evidence that prenatal alcohol exposure (PAE) can lead to a wide range of impairments in cognitive, social and emotional behaviors, drinking during pregnancy remains common. Although there is a general understanding that high levels of drinking during pregnancy are unsafe, conflicting evidence regarding the impact of low intake may account for the persistence of this behavior. Methods In order to investigate the effects of PAE on learning and executive control we utilized a voluntary paradigm where pregnant mice had access to a saccharin sweetened 10% alcohol solution for 4 hours, during the dark cycle, throughout gestation. Male and female offspring were tested as adults on a touch-screen discrimination and reversal task mediated by corticostriatal circuits. Results Consistent with previous findings, PAE did not lead to gross morphological, motor or sensory alterations in offspring. Both PAE and saccharin control female mice were slower to acquire the discrimination than males, but PAE did not impair associative learning in either sex. During reversal, PAE led to a specific and significant impairment in the early phase, where cortical control is most required to flexibly alter choice behavior. PAE mice showed a significant increase in maladaptive perseverative responses but showed intact learning of the new association during late reversal. Conclusions Previously, data from clinical studies have suggested that executive control deficits may underlie cognitive, as well as social, problems seen in adolescents with documented PAE. These data demonstrate that even more moderate alcohol exposure during development can lead to impaired cognitive functioning well into adulthood. PMID:25581651

  6. Treatment Concerns and Functional Impairment in Pediatric Anxiety.

    PubMed

    Wu, Monica S; Salloum, Alison; Lewin, Adam B; Selles, Robert R; McBride, Nicole M; Crawford, Erika A; Storch, Eric A

    2016-08-01

    Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment. PMID:26438217

  7. Microbial colonization and lung function in adolescents with cystic fibrosis.

    PubMed

    Hector, Andreas; Kirn, Tobias; Ralhan, Anjali; Graepler-Mainka, Ute; Berenbrinker, Sina; Riethmueller, Joachim; Hogardt, Michael; Wagner, Marlies; Pfleger, Andreas; Autenrieth, Ingo; Kappler, Matthias; Griese, Matthias; Eber, Ernst; Martus, Peter; Hartl, Dominik

    2016-05-01

    With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. PMID:26856310

  8. Lung function in post-poliomyelitis syndrome: a cross-sectional study*

    PubMed Central

    de Lira, Claudio Andre Barbosa; Minozzo, Fábio Carderelli; Sousa, Bolivar Saldanha; Vancini, Rodrigo Luiz; Andrade, Marília dos Santos; Quadros, Abrahão Augusto Juviniano; Oliveira, Acary Souza Bulle; da Silva, Antonio Carlos

    2013-01-01

    OBJECTIVE: To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls. METHODS: Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment). RESULTS: The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups. CONCLUSIONS: With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function. PMID:24068267

  9. Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+ T-Cell Responses to Mycobacteria

    PubMed Central

    Banda, Dominic H.; Afran, Louise; Kankwatira, Anstead M.; Malamba, Rose D.; Allain, Theresa J.; Gordon, Stephen B.; Heyderman, Robert S.; Russell, David G.

    2014-01-01

    Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4+ T-cell responses observed in HIV-infected ART-naive adults. Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4+ T-cell responses to Mycobacterium in HIV-infected individuals. Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4+ T-cell responses were measured by intracellular cytokine staining. Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4+ T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4+ T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4+ T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4+ T-cell responses were impaired in adults on ART irrespective of duration. Conclusions: AM and mycobacteria-specific alveolar CD4+ T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated. PMID:25225948

  10. Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments

    PubMed Central

    Zhou, Xia; Hu, Xiaopeng; Zhang, Chao; Wang, Haibao; Zhu, Xiaoqun; Xu, Liyan; Sun, Zhongwu; Yu, Yongqiang

    2016-01-01

    Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations

  11. Validating Excised Rodent Lungs for Functional Hyperpolarized Xenon-129 MRI

    PubMed Central

    Lilburn, David M. L.; Hughes-Riley, Theodore; Six, Joseph S.; Stupic, Karl F.; Shaw, Dominick E.; Pavlovskaya, Galina E.; Meersmann, Thomas

    2013-01-01

    Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies. PMID:24023683

  12. Impaired functional integration in multiple sclerosis: a graph theory study.

    PubMed

    Rocca, Maria A; Valsasina, Paola; Meani, Alessandro; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2016-01-01

    Aim of this study was to explore the topological organization of functional brain network connectivity in a large cohort of multiple sclerosis (MS) patients and to assess whether its disruption contributes to disease clinical manifestations. Graph theoretical analysis was applied to resting state fMRI data from 246 MS patients and 55 matched healthy controls (HC). Functional connectivity between 116 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Global network properties (network degree, global efficiency, hierarchy, path length and assortativity) were abnormal in MS patients vs HC, and contributed to distinguish cognitively impaired MS patients (34%) from HC, but not the main MS clinical phenotypes. Compared to HC, MS patients also showed: (1) a loss of hubs in the superior frontal gyrus, precuneus and anterior cingulum in the left hemisphere; (2) a different lateralization of basal ganglia hubs (mostly located in the left hemisphere in HC, and in the right hemisphere in MS patients); and (3) a formation of hubs, not seen in HC, in the left temporal pole and cerebellum. MS patients also experienced a decreased nodal degree in the bilateral caudate nucleus and right cerebellum. Such a modification of regional network properties contributed to cognitive impairment and phenotypic variability of MS. An impairment of global integration (likely to reflect a reduced competence in information exchange between distant brain areas) occurs in MS and is associated with cognitive deficits. A regional redistribution of network properties contributes to cognitive status and phenotypic variability of these patients. PMID:25257603

  13. Functional MRI in investigating cognitive impairment in multiple sclerosis.

    PubMed

    Rocca, M A; De Meo, E; Filippi, M

    2016-09-01

    There is increasing evidence that the severity of the clinical manifestations of multiple sclerosis (MS) does not simply result from the extent of tissue destruction, but it rather represents a complex balance between tissue damage, tissue repair, and cortical reorganization. Functional magnetic resonance imaging (fMRI) provides information about the plasticity of the human brain. Therefore, it has the potential to provide important pieces of information about brain reorganization following MS-related structural damage. When investigating cognitive systems, fMRI changes have been described in virtually all patients with MS and different clinical phenotypes. These functional changes have been related to the extent of brain damage within and outside T2-visible lesions as well as to the involvement of specific central nervous system structures. It has also been suggested that a maladaptive recruitment of specific brain regions might be associated with the appearance of clinical symptoms in MS, such as fatigue and cognitive impairment. fMRI studies from clinically (and cognitively) impaired MS patients may be influenced by different task performances between patients and controls. As a consequence, new strategies have been introduced to assess the role, if any, of brain reorganization in severely impaired patients, including the analysis of resting-state networks. The enhancement of any beneficial effects of this brain adaptive plasticity should be considered as a potential target of therapy for MS. PMID:27580905

  14. Partial liquid ventilation improves lung function in ventilation-induced lung injury.

    PubMed

    Vazquez de Anda, G F; Lachmann, R A; Verbrugge, S J; Gommers, D; Haitsma, J J; Lachmann, B

    2001-07-01

    Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation. PMID:11510811

  15. Assessing Depression Related Severity and Functional Impairment: The Overall Depression Severity and Impairment Scale (ODSIS)

    PubMed Central

    Ito, Masaya; Bentley, Kate H.; Oe, Yuki; Nakajima, Shun; Fujisato, Hiroko; Kato, Noriko; Miyamae, Mitsuhiro; Kanie, Ayako; Horikoshi, Masaru; Barlow, David H.

    2015-01-01

    Background The Overall Depression Severity and Impairment Scale (ODSIS) is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis. Methods From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive–compulsive disorder, and 371 non-clinical panelists). Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation. Results Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test–retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately. Conclusions This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity. PMID:25874558

  16. Junctional Adhesion Molecule A Promotes Epithelial Tight Junction Assembly to Augment Lung Barrier Function

    PubMed Central

    Mitchell, Leslie A.; Ward, Christina; Kwon, Mike; Mitchell, Patrick O.; Quintero, David A.; Nusrat, Asma; Parkos, Charles A.; Koval, Michael

    2016-01-01

    Epithelial barrier function is maintained by tight junction proteins that control paracellular fluid flux. Among these proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein. To assess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA. In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepithelial resistance, decreased expression of the tight junction scaffold protein zonula occludens 1, and disrupted junctional localization of the structural transmembrane protein claudin-18. Consistent with findings in other organs, loss of JAM-A decreased β1 integrin expression and impaired filamentous actin formation. Using a model of mild systemic endoxotemia induced by i.p. injection of lipopolysaccharide, we report that JAM-A−/− mice showed increased susceptibility to pulmonary edema. On injury, the enhanced susceptibility of JAM-A−/− mice to edema correlated with increased, transient disruption of claudin-18, zonula occludens 1, and zonula occludens 2 localization to lung tight junctions in situ along with a delay in up-regulation of claudin-4. In contrast, wild-type mice showed no change in lung tight junction morphologic features in response to mild systemic endotoxemia. These findings support a key role of JAM-A in promoting tight junction homeostasis and lung barrier function by coordinating interactions among claudins, the tight junction scaffold, and the cytoskeleton. PMID:25438062

  17. Alterations in Lung Functions Based on BMI and Body Fat % Among Obese Indian Population at National Capital Region

    PubMed Central

    Kamal, Ritul; Bihari, Vipin; Sathian, Brijesh; Srivastava, Anup Kumar

    2015-01-01

    Background In India, non-asthmatic hospital admission case study has been conducted to find out the relationship between obesity and lung functions. The main objective of the present study was to find out the alterations in lung functions due to obesity among Indian population living at National Capital Region (NCR). Materials and Methods We examined 609 non obese and 211 obese subjects in a cross sectional study from National Capital Region, India with age group ranges between 18-70 years. BMI and body fat % was determined using body fat analyzer. Obese and non-obese subjects were classified based on criteria for BMI and Body fat %. Lung function test viz., FEV1 and PEFR were conducted using portable spirometer (PIKO-1). Results A significant correlation (p<0.05) was observed between BMI and PEFR among non-obese male and female subjects. Decline in PEFR and FEV1 values for corresponding increase in body fat % was observed among study subjects. A significant (p<0.01) decline in mean FEV1 and PEFR was observed among non-obese and obese subjects, compared to their Indian reference standards for lung functions. A significant negative correlation (p<0.01) was observed between body fat % and lung functions (FEV1, PEFR). Conclusion It is concluded that obese subjects are at a risk of lung function impairment, based on the criteria followed for BMI and body fat %. The study also demonstrate that body fat% classification as a better index for determination of obese subjects compared to BMI classification, with respect to lung function impairments. PMID:26913206

  18. Effects of air pollution on lung function and symptoms of asthma, rhinitis and eczema in primary school children.

    PubMed

    Altuğ, Hicran; Gaga, Eftade O; Döğeroğlu, Tuncay; Ozden, Ozlem; Ornektekin, Sermin; Brunekreef, Bert; Meliefste, Kees; Hoek, Gerard; Van Doorn, Wim

    2013-09-01

    Health effects of ambient air pollution were studied in three groups of schoolchildren living in areas (suburban, urban and urban-traffic) with different air pollution levels in Eskişehir, Turkey. This study involved 1,880 students aged between 9 and 13 years from 16 public primary schools. This two-season study was conducted from January 2008 through March 2009. Symptoms of asthma, rhinitis and eczema were determined by the International Study of Asthma and Allergies in Childhood questionnaire in 2008. Two lung function tests were performed by each child for summer and winter seasons with simultaneous ambient air measurements of ozone (O3), nitrogen dioxide (NO2) and sulfur dioxide (SO2) by passive sampling. Effects of air pollution on impaired lung function and symptoms in schoolchildren were estimated by multivariate logistic regression analyses. Girls with impaired lung function (only for the summer season evaluation) were more observed in suburban and urban areas when compared to urban-traffic area ([odds ratio (OR) = 1.49; 95 % confidence interval (CI) 1.04-2.14] and [OR = 1.69 (95 % CI 1.06-2.71)] for suburban vs. urban-traffic and urban vs. urban-traffic, respectively). Significant association between ambient ozone concentrations and impaired lung function (for an increase of 10 μg m(-3)) was found only for girls for the summer season evaluation [OR = 1.11 (95 % CI 1.03-1.19)]. No association was found for boys and for the winter season evaluation. No association was found between any of the measured air pollutants and symptoms of current wheeze, current rhinoconjunctivitis and current itchy rash. The results of this study showed that increasing ozone concentrations may cause a sub-acute impairment in lung function of school aged children. PMID:23591930

  19. Impairments that Influence Physical Function among Survivors of Childhood Cancer

    PubMed Central

    Wilson, Carmen L.; Gawade, Prasad L.; Ness, Kirsten K.

    2015-01-01

    Children treated for cancer are at increased risk of developing chronic health conditions, some of which may manifest during or soon after treatment while others emerge many years after therapy. These health problems may limit physical performance and functional capacity, interfering with participation in work, social, and recreational activities. In this review, we discuss treatment-induced impairments in the endocrine, musculoskeletal, neurological, and cardiopulmonary systems and their influence on mobility and physical function. We found that cranial radiation at a young age was associated with a broad range of chronic conditions including obesity, short stature, low bone mineral density and neuromotor impairments. Anthracyclines and chest radiation are associated with both short and long-term cardiotoxicity. Although numerous chronic conditions are documented among individuals treated for childhood cancer, the impact of these conditions on mobility and function are not well characterized, with most studies limited to survivors of acute lymphoblastic leukemia and brain tumors. Moving forward, further research assessing the impact of chronic conditions on participation in work and social activities is required. Moreover, interventions to prevent or ameliorate the loss of physical function among children treated for cancer are likely to become an important area of survivorship research. PMID:25692094

  20. The Early Indicators of Functional Decrease in Mild Cognitive Impairment

    PubMed Central

    Kubicki, Alexandre; Fautrelle, Lilian; Bourrelier, Julien; Rouaud, Olivier; Mourey, France

    2016-01-01

    Objectives: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity in muscle synergies involved in an arm-pointing movement in functionally unimpaired MCI patients. We hypothesized that early motor indicators exist in this population at a preclinical level. Methods: Electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Older Adults (OA), and MCI patients. The OA and MCI groups presented the same functional status. Each subject performed 20 arm-pointing movements from a standing position. Results: The main differences were (1) an earlier activation of the left Obliquus internus in MCI compared with OA group, (2) an earlier activation for the MCI compared with both OA and YA. The temporal differences in muscle synergies between MCI and OA groups were linked with executive functions of MCI patients, assessed by the trail making test. Moreover, the results show a delayed activation of the right Biceps Femoris and the right Erector Spinae at l3 in MCI and OA compared with YA. Interpretation: The motor program changes highlighted in our patient MCI group suggest that discrete modifications of the motor command seem to exist even in the absence of functional impairment. Instead of showing an indication of delayed muscle activation in the MCI patients, our results highlight some early activation of several trunk muscles. PMID:27570509

  1. [Lung function changes during anesthesia and thoracic surgery].

    PubMed

    Bigler, Dennis R

    2003-01-13

    After anaesthesia and thorax surgery, a significant reduction in pulmonary function with up to a 50% decrease in FEV1, FVC, and FRC is seen, leading to a high risk of atelectasis and hypoxia, and therefore making respiratory complications the major course of perioperative morbidity and mortality in this group of patients. This severe reduction in lung function gradually diminishes within three weeks, but postoperative pain and sedation increase the deterioration in lung function, and treatment is therefore based on anaesthetic drugs with a short elimination time and effective postoperative pain treatment with epidural analgesia or other regional blockade, and minimal use of opioids. Together with more sparing surgical methods, it is possible to operate on patients with severely reduced preoperative lung function (FEV1 = 0.651 or 22% of predicted value) with lung resection and immediate extubation. A reduction in pulmonary complications after thoracic surgery from 25-30% down to 10-15% is also seen, depending on age and preoperative lung function. PMID:12555706

  2. Surgical trauma and immune functional changes following major lung resection.

    PubMed

    Ng, Calvin S H; Lau, Kelvin K W

    2015-02-01

    Video-assisted thoracic surgery (VATS) has evolved greatly over the last two decades. VATS major lung resection for early stage non-small cell lung carcinoma (NSCLC) has been shown to result in less postoperative pain, less pulmonary dysfunction postoperatively, shorter hospital stay, and better patient tolerance to adjuvant chemotherapy compared with patients who underwent thoracotomy. Several recent studies have even reported improved long-term survival in those who underwent VATS major lung resection for early stage NSCLC when compared with open technique. Interestingly, the immune status and autologous tumor killing ability of lung cancer patients have previously been associated with long-term survival. VATS major lung resection can result in an attenuated postoperative inflammatory response. Furthermore, the minimal invasive approach better preserve patients' postoperative immune function, leading to higher circulating natural killer and T cells numbers, T cell oxidative activity, and levels of immunochemokines such as insulin growth factor binding protein 3 following VATS compared with thoracotomy. Apart from host immunity, the angiogenic environment following surgery may also have a role in determining cancer recurrence and possibly survival. Whether differences in immunological and biochemical mediators contribute significantly towards improved clinical outcomes following VATS major lung resection for lung cancer remains to be further investigated. Future studies will also need to address whether the reduced access trauma from advanced thoracic surgical techniques, such as single-port VATS, can further attenuate the postoperative inflammatory response. PMID:25829712

  3. The Nature of Elder Impairment and Its Impact on Family Caregivers' Health and Psychosocial Functioning.

    ERIC Educational Resources Information Center

    Cattanach, Lynn; Tebes, Jacob Kraemer

    1991-01-01

    Assessed nature of elder impairment and its impact on health and psychosocial functioning of 102 family caregivers. Found no differences among caregivers of cognitively impaired, functionally impaired, and nonimpaired elderly relatives in terms of self-reported health or psychosocial functioning. Suggests that other aspects of caregiving context…

  4. Balance Functional Assessment in People with Visual Impairment

    PubMed Central

    Rutkowska, Izabela; Bednarczuk, Grzegorz; Molik, Bartosz; Morgulec-Adamowicz, Natalia; Marszałek, Jolanta; Kaźmierska-Kowalewska, Kalina; Koc, Krzysztof

    2015-01-01

    The aims of this study were twofold: to assess the level of balance of people with visual impairment against the BOT-2 standard scores for the able-bodied, and to identify in which trials subjects had the greatest difficulties in maintaining balance with respect to the degree of vision loss and age categories. One hundred twenty-seven subjects with visual impairment aged 6–16 years, participated in the study (68 girls and 59 boys). The division for partially sighted people (61) and the blind (66) was made according to the WHO classification. Functional balance assessment was made using a balance subtest from the Bruininks-Oseretsky test. Significant relationships were noticed between age and the level of balance (χ2 = 8.35 p <0,05), as well as between the degree of vision loss and the level of balance (χ2 = 24.53 p <0,001). The level of balance of almost all blind subjects was below (20%) or well-below (60%) the average for the able-bodied. The subjects’ ability to maintain balance was not dependent on gender and was associated primarily with the degree of visual impairment and age. Partially sighted people had better balance than the blind and the decrease in visual acuity resulted in reduction of balance skills. The lowest level of balance was observed in blind students aged 7–11 years. Elaborating physical fitness improvement programs for children and adolescents with visual impairment, diversity of age, the degree of vision loss and limitations of ablility to maintain balance should be taken into account. PMID:26834878

  5. Balance Functional Assessment in People with Visual Impairment.

    PubMed

    Rutkowska, Izabela; Bednarczuk, Grzegorz; Molik, Bartosz; Morgulec-Adamowicz, Natalia; Marszałek, Jolanta; Kaźmierska-Kowalewska, Kalina; Koc, Krzysztof

    2015-11-22

    The aims of this study were twofold: to assess the level of balance of people with visual impairment against the BOT-2 standard scores for the able-bodied, and to identify in which trials subjects had the greatest difficulties in maintaining balance with respect to the degree of vision loss and age categories. One hundred twenty-seven subjects with visual impairment aged 6-16 years, participated in the study (68 girls and 59 boys). The division for partially sighted people (61) and the blind (66) was made according to the WHO classification. Functional balance assessment was made using a balance subtest from the Bruininks-Oseretsky test. Significant relationships were noticed between age and the level of balance (χ2 = 8.35 p <0,05), as well as between the degree of vision loss and the level of balance (χ2 = 24.53 p <0,001). The level of balance of almost all blind subjects was below (20%) or well-below (60%) the average for the able-bodied. The subjects' ability to maintain balance was not dependent on gender and was associated primarily with the degree of visual impairment and age. Partially sighted people had better balance than the blind and the decrease in visual acuity resulted in reduction of balance skills. The lowest level of balance was observed in blind students aged 7-11 years. Elaborating physical fitness improvement programs for children and adolescents with visual impairment, diversity of age, the degree of vision loss and limitations of ablility to maintain balance should be taken into account. PMID:26834878

  6. Mitochondrial dysfunction impairs tumor suppressor p53 expression/function.

    PubMed

    Compton, Shannon; Kim, Chul; Griner, Nicholas B; Potluri, Prasanth; Scheffler, Immo E; Sen, Sabyasachi; Jerry, D Joseph; Schneider, Sallie; Yadava, Nagendra

    2011-06-10

    Recently, mitochondria have been suggested to act in tumor suppression. However, the underlying mechanisms by which mitochondria suppress tumorigenesis are far from being clear. In this study, we have investigated the link between mitochondrial dysfunction and the tumor suppressor protein p53 using a set of respiration-deficient (Res(-)) mammalian cell mutants with impaired assembly of the oxidative phosphorylation machinery. Our data suggest that normal mitochondrial function is required for γ-irradiation (γIR)-induced cell death, which is mainly a p53-dependent process. The Res(-) cells are protected against γIR-induced cell death due to impaired p53 expression/function. We find that the loss of complex I biogenesis in the absence of the MWFE subunit reduces the steady-state level of the p53 protein, although there is no effect on the p53 protein level in the absence of the ESSS subunit that is also essential for complex I assembly. The p53 protein level was also reduced to undetectable levels in Res(-) cells with severely impaired mitochondrial protein synthesis. This suggests that p53 protein expression is differentially regulated depending upon the type of electron transport chain/respiratory chain deficiency. Moreover, irrespective of the differences in the p53 protein expression profile, γIR-induced p53 activity is compromised in all Res(-) cells. Using two different conditional systems for complex I assembly, we also show that the effect of mitochondrial dysfunction on p53 expression/function is a reversible phenomenon. We believe that these findings will have major implications in the understanding of cancer development and therapy. PMID:21502317

  7. Cadaver lung donors: effect of preharvest ventilation on graft function.

    PubMed

    Ulicny, K S; Egan, T M; Lambert, C J; Reddick, R L; Wilcox, B R

    1993-05-01

    The pulmonary donor pool would increase substantially if lungs could be safely transplanted after cessation of circulation. To determine whether ventilation of cadaver lungs could improve graft function, canine donors were sacrificed and then ventilated with 100% oxygen (n = 6) or 100% nitrogen (n = 6); 6 served as nonventilated controls. Four hours after death, the lungs were flushed with modified Euro-Collins solution and harvested. Controls were ventilated with 100% oxygen only during flush and harvest. Recipients were rendered dependent on the transplanted lung by occlusion of the right pulmonary artery and bronchus 1 hour after transplantation. Ventilation was maintained at a constant inspired oxygen fraction of 0.4. Four controls died of pulmonary edema shortly after occlusion of the native lung. The mean arterial oxygen tensions in the oxygen-ventilated, nitrogen-ventilated, and control groups at the end of 8 hours were 81 mm Hg (n = 4), 88 mm Hg (n = 3), and 55 mm Hg (n = 2), respectively. Postmortem oxygen ventilation improved early recipient survival and gas exchange. Postmortem nitrogen ventilation improved early gas exchange and delayed recipient death compared with non-ventilated controls. The mechanics of ventilation appears to confer a functional advantage independent of a continued supply of oxygen. Transplantation of lungs harvested from cadavers after cessation of circulation might be feasible. PMID:8494430

  8. Hyperpolarized helium-3 mouse lung MRI: Studies of lung structure and function

    NASA Astrophysics Data System (ADS)

    Dugas, Joseph Paul

    Hyperpolarized 3He magnetic resonance imaging (MRI) of human and animal lungs has displayed promising and useful applications to studies of lung structure and function in both healthy and diseased lungs. Hyperpolarized 3He MRI allows the visualization of gas in the gas-exchange spaces of the lungs (as opposed to tissue) and has proven especially effective in studying diseases that are characterized by ventilation defects, such as emphysema. In particular, in-vivo measurements of the 3He apparent diffusion coefficient (ADC) can quantify lung structure by measuring its restrictive effects on the motion of 3He spins. This allows for detection and longitudinal tracking of changes in micro-architecture that result from disease destruction of alveolar walls. Due, in part, to the difficulties inherent in administering and imaging hyperpolarized 3He within the small (0.5 cc volume) mouse lung, applications of hyperpolarized 3He MRI techniques to laboratory mice are scarce. We have been able to implement and improve the techniques of hyperpolarized 3He mouse lung MRI and subsequently apply them to studies of several mouse models of disease, including elastase-induced emphysema, smoking-induced emphysema, and lung cancer. Here we detail the design, development, and implementation of a versatile, electronically-controlled, small animal ventilator that is capable of delivering tiny volumes of hyperpolarized 3He, mixed with oxygen, to the mouse and is also compatible with both the easily depolarized 3He gas and the highly magnetic environment within and around an imaging magnet. Also described are NM techniques developed to improve the signal-to-noise ratio of our images and effectively utilize the gas hyperpolarization. Applications of these technologies and techniques to small animal models of disease are presented wherein we have measured up to a 35% increase in 3He ADC in mice with elastase-induced emphysema as compared to healthy mice. We also demonstrate the potential

  9. Functions and mechanisms of long noncoding RNAs in lung cancer

    PubMed Central

    Peng, Zhenzi; Zhang, Chunfang; Duan, Chaojun

    2016-01-01

    Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs) are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field. PMID:27499635

  10. The optical properties of lung as a function of respiration

    NASA Astrophysics Data System (ADS)

    Beek, J. F.; van Staveren, H. J.; Posthumus, P.; Sterenborg, H. J. C. M.; van Gemert, M. J. C.

    1997-11-01

    Lung consists of alveoli enclosed by tissue and both structures contribute to volume-dependent scattering of light. It is the purpose of this paper to determine the volume-dependent optical properties of lung. In vivo interstitial fibre measurements of the effective attenuation coefficient at 632.8 nm differed during inspiration from that during expiration . In vitro measurements on a piglet lung insufflated with oxygen from 50 to 150 ml showed the effective attenuation coefficient at 632.8 nm decreases as a function of oxygen volume in the lung (at 50 ml , at 100 ml , and at 150 ml ). This was explained by combining scattering of alveoli (Mie theory) with optical properties of collapsed lung tissue using integrating sphere measurements. Theory and measured in vitro values showed good agreement (deviation ). Combination of these data yields the absorption coefficient and scattering parameters of lung tissue as a function of lung volume. We conclude that the light fluence rate in lung tissue should be estimated using optical properties that include scattering by the alveoli.

  11. Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

    PubMed Central

    Yao, Jianhua; Jones, Amanda M.; Julien-Williams, Patricia; Stylianou, Mario; Moss, Joel

    2014-01-01

    Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (−2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (−2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (−1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. PMID:25329516

  12. Normalization of lung function following treatment of secondary usual interstitial pneumonia: a case report.

    PubMed

    Hohberger, Laurie A; Montero-Arias, Felicia; Roden, Anja C; Vassallo, Robert

    2015-01-01

    Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient's symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy. PMID:25922588

  13. Normalization of Lung Function Following Treatment of Secondary Usual Interstitial Pneumonia: A Case Report

    PubMed Central

    Hohberger, Laurie A; Montero-Arias, Felicia; Roden, Anja C; Vassallo, Robert

    2015-01-01

    Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient’s symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy. PMID:25922588

  14. Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD.

    PubMed

    Neder, J Alberto; Alharbi, Abdullah; Berton, Danilo C; Alencar, Maria Clara N; Arbex, Flavio F; Hirai, Daniel M; Webb, Katherine A; O'Donnell, Denis E

    2016-08-01

    Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO2 output (VCO2) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO2 nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan-Meier analyses showed that survival time was particularly reduced when ventilation/VCO2 nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease. PMID:27077955

  15. Altered Lung Function Test in Asymptomatic Women Using Biomass Fuel for Cooking

    PubMed Central

    2014-01-01

    Background: One third of the world’s population use biomass fuel like wood, dung or charcoal for cooking. The smoke from these organic materials increases the incidence of respiratory illness including chronic obstructive pulmonary disease and lung cancer. Aim: To evaluate forced expiratory lung volumes in asymptomatic women previously exposed to biomass fuel smoke. Materials and Methods: The study was done in 74 healthy asymptomatic women divided into two age matched groups of 37 each. Pulmonary function tests (PFT) were assessed by computerised spirometry and statistical comparisons done on women using biomass fuel (study group) and women using other sources of fuel (LPG/ electric stove) for cooking (control group). Results: The PFT results showed significant reduction in forced expiratory lung volumes like Forced Vital Capacity (FVC), Forced Expiratory Volume in 1st sec (FEV1), Forced Expiratory Flow between 25-75% (FEF 25-75%) and Forced Expiratory Volume percentage (FEV1%) in biomass fuel users as compared to those not exposed to biomass fuel smoke. Conclusion: The results of this study suggest that biomass fuel smoke may produce definite impairment in lung function, especially with regard to the smaller airways. PMID:25478331

  16. Impaired Serotonergic Brainstem Function during and after Seizures

    PubMed Central

    Zhan, Qiong; Buchanan, Gordon F.; Motelow, Joshua E.; Andrews, John; Vitkovskiy, Petr; Chen, William C.; Serout, Florian; Gummadavelli, Abhijeet; Kundishora, Adam; Furman, Moran; Li, Wei; Bo, Xiao; Richerson, George B.

    2016-01-01

    Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal. However, direct demonstration of seizure-associated neuronal activity changes in brainstem serotonergic regions has been lacking. Here, we performed multiunit and single-unit recordings from medullary raphe and midbrain dorsal raphe nuclei in an established rat seizure model while measuring changes in breathing rate and depth as well as heart rate. Serotonergic neurons were identified by immunohistochemistry. Respiratory rate, tidal volume, and minute ventilation were all significantly decreased during and after seizures in this model. We found that population firing of neurons in the medullary and midbrain raphe on multiunit recordings was significantly decreased during the ictal and post-ictal periods. Single-unit recordings from identified serotonergic neurons in the medullary raphe revealed highly consistently decreased firing during and after seizures. In contrast, firing of midbrain raphe serotonergic neurons was more variable, with a mixture of increases and decreases. The markedly suppressed firing of medullary serotonergic neurons supports their possible role in simultaneously impaired cardiorespiratory function in seizures. Decreased arousal likely arises from depressed population activity of several neuronal pools in the upper brainstem and forebrain. These findings have important implications for preventing morbidity and mortality in people living with epilepsy. SIGNIFICANCE STATEMENT Seizures often cause impaired breathing, cardiac dysfunction, and loss of consciousness. The brainstem and

  17. Heterogeneous ventilation and perfusion: a sensitive indicator of lung impairment in nonsmoking coal miners.

    PubMed

    Susskind, H; Acevedo, J C; Iwai, J; Rasmussen, D L; Heydinger, D K; Pate, H R; Harold, W H; Brill, A B

    1988-03-01

    Twenty life-long nonsmoking West Virginia coal-miners participated in a study to amplify the role of focal irregularities on regional ventilation (V) and perfusion (Q) and to develop an improved method for the early detection of coal-workers' pneumoconiosis. Their mean age was 59.3 yr and they averaged 35.2 years' exposure to coal dust. Conventional pulmonary function tests were supplemented by measurement of V, Q and lung volume (V), using radioactive Kr-81m, Tc-99m MAA and Xe-127, respectively, to determine regional abnormalities in lung function. A computer analysis of the regional distributions of V/V, Q/V and V/Q was performed, and their topographical distributions and indices of heterogeneity (HI) computed. V/V and Q/V were significantly reduced in the lower third, and increased in the upper two-thirds of the miners' lungs; V/Q was reduced in the upper half. The miners' V/V and Q/V were more heterogeneous (p less than 0.001) than that of eleven age-matched controls, with mean ventilation HI values of 0.190 +/- 0.027 and 0.133 +/- 0.011, respectively, and mean perfusion HI values of 0.206 +/- 0.022 and 0.164 +/- 0.041, respectively. P(A-a)O2 correlated positively (r = 0.72; p less than 0.001) with ventilation HI. Gas exchange was the most significant functional measurement, being abnormal in 19/20 subjects. In contrast, conventional spirometric measurements were within the predicted normal limits in all but four miners. PMID:3384076

  18. Pharmacotherapy of impaired mucociliary clearance in non-CF pediatric lung disease. A review of the literature.

    PubMed

    Boogaard, Ruben; de Jongste, Johan C; Merkus, Peter J F M

    2007-11-01

    Mucoactive agents are used to treat a variety of lung diseases involving impaired mucociliary clearance or mucus hypersecretion. The mucoactive agents studied most frequently are N-acetylcysteine (NAC), recombinant human DNase (rhDNase), and hypertonic saline. Studies on the efficacy of these have been mainly conducted in adults, and in patients with cystic fibrosis (CF). The exact role of mucoactive agents in children with non-CF lung disease is not well established. We present an overview of the current literature reporting clinical outcome measures of treatment with NAC, rhDNase, and hypertonic saline in children. PMID:17902149

  19. Integrative pathway genomics of lung function and airflow obstruction.

    PubMed

    Gharib, Sina A; Loth, Daan W; Soler Artigas, María; Birkland, Timothy P; Wilk, Jemma B; Wain, Louise V; Brody, Jennifer A; Obeidat, Ma'en; Hancock, Dana B; Tang, Wenbo; Rawal, Rajesh; Boezen, H Marike; Imboden, Medea; Huffman, Jennifer E; Lahousse, Lies; Alves, Alexessander C; Manichaikul, Ani; Hui, Jennie; Morrison, Alanna C; Ramasamy, Adaikalavan; Smith, Albert Vernon; Gudnason, Vilmundur; Surakka, Ida; Vitart, Veronique; Evans, David M; Strachan, David P; Deary, Ian J; Hofman, Albert; Gläser, Sven; Wilson, James F; North, Kari E; Zhao, Jing Hua; Heckbert, Susan R; Jarvis, Deborah L; Probst-Hensch, Nicole; Schulz, Holger; Barr, R Graham; Jarvelin, Marjo-Riitta; O'Connor, George T; Kähönen, Mika; Cassano, Patricia A; Hysi, Pirro G; Dupuis, Josée; Hayward, Caroline; Psaty, Bruce M; Hall, Ian P; Parks, William C; Tobin, Martin D; London, Stephanie J

    2015-12-01

    Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease. PMID:26395457

  20. A peptide that inhibits function of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) reduces lung cancer metastasis

    PubMed Central

    Chen, C-H; Thai, P; Yoneda, K; Adler, KB; Yang, P-C; Wu, R

    2015-01-01

    Myristoylated Alanine-Rich C Kinase Substrate (MARCKS), a substrate of protein kinase C, is a key regulatory molecule controlling mucus granule secretion by airway epithelial cells as well as directed migration of leukocytes, stem cells and fibroblasts. Phosphorylation of MARKCS may be involved in these responses. However, the functionality of MARCKS and its related phosphorylation in lung cancer malignancy have not been characterized. This study demonstrated elevated levels of MARCKS and phospho-MARCKS in highly invasive lung cancer cell lines and lung cancer specimens from non-small-cell lung cancer patients. siRNA knockdown of MARCKS expression in these highly invasive lung cancer cell lines reduced cell migration and suppressed PI3K (phosphatidylinositol 3′-kinase)/Akt phosphorylation and Slug level. Interestingly, treatment with a peptide identical to the MARCKS N-terminus sequence (the MANS peptide) impaired cell migration in vitro and also the metastatic potential of invasive lung cancer cells in vivo. Mechanistically, MANS peptide treatment resulted in a coordination of increase of E-cadherin expression, suppression of MARCKS phosphorylation and AKT/Slug signalling pathway but not the expression of total MARCKS. These results indicate a crucial role for MARCKS, specifically its phosphorylated form, in potentiating lung cancer cell migration/metastasis and suggest a potential use of MARCKS-related peptides in the treatment of lung cancer metastasis. PMID:23955080

  1. Does perinatal asphyxia impair cognitive function without cerebral palsy?

    PubMed Central

    Gonzalez, F F; Miller, S P

    2006-01-01

    Some studies on neurodevelopmental outcomes after neonatal encephalopathy have suggested that cognitive deficits do not occur in the absence of cerebral palsy. It is increasingly apparent that childhood survivors of overt neonatal encephalopathy may have cognitive impairments, even in the absence of functional motor deficits. The risk of cognitive deficits is related to the severity of neonatal encephalopathy and the pattern of brain injury on neuroimaging, particularly the watershed pattern of injury. A better understanding of the risk factors for cognitive abnormalities after neonatal encephalopathy will ultimately lead to interventions to prevent these deficits. Identifying the full spectrum of neurodevelopmental outcomes after neonatal encephalopathy will also allow care givers to identify children requiring early intervention to maximise their potential for independent function throughout development. PMID:17056843

  2. Structural Equation Modeling of Motor Impairment, Gross Motor Function, and the Functional Outcome in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Park, Eun-Young; Kim, Won-Ho

    2013-01-01

    Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study…

  3. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  4. Lung function in West Sussex firemen: a four year study.

    PubMed

    Horsfield, K; Guyatt, A R; Cooper, F M; Buckman, M P; Cumming, G

    1988-02-01

    Although firefighting is a hazardous occupation, published evidence of long-term lung damage in firemen is inconsistent. A group of 96 men from the West Sussex Fire Brigade, which covers a simi-rural, semi-urban area, were followed up for between one and four years. They included 31 non-smokers, 40 smokers, and 25 ex-smokers. After four years 12 firemen had been lost to the study. A control group of 69 volunteers, consisting of non-smoking men from various other occupations, were followed up in parallel. Lung function tests, covering a wider range than has been previously used in similar studies, were repeated six monthly for two years and annually for a further two years. The results were expressed in terms of the rate of change with time of the lung function variables. Many of the variables deteriorated in both firemen and controls, but the rate of deterioration was greater in the controls than the firemen for vital capacity, ratio of residual volume to total lung capacity, FEV1, FVC, peak expiratory flow (PEF), flow at 50% and 25% remaining vital capacity (V50 and V25 respectively), and airways resistance (Raw). With respect to PEF, V50, V25, and Raw the control subjects deteriorated more rapidly even than the smokers and ex-smokers among the firemen. Alveolar mixing efficiency (AME), a measure of small airways function, did not change significantly over the study period in any group. Non-smoking firemen had the highest mean value of AME, decreasing through ex-smokers, controls, and smokers. We conclude that these results show no evidence of chronic lung damage in West Sussex firemen; indeed, the firemen as a group show a lower rate of deterioration of lung function with age than do the control subjects. This is attributed to the selection of fit men for the service, continued physical training, and the regular use of breathing apparatus. PMID:3342193

  5. Updates on Functional Characterization of Bronchopulmonary Dysplasia – The Contribution of Lung Function Testing

    PubMed Central

    Greenough, Anne; Pahuja, Anoop

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is a chronic lung disease that predominantly affects prematurely born infants. Initially, BPD was described in infants who had suffered severe respiratory failure and required high pressure, mechanical ventilation with high concentrations of supplementary oxygen. Now, it also occurs in very prematurely born infants who initially had minimal or even no signs of lung disease. These differences impact the nature of the lung function abnormalities suffered by “BPD” infants, which are also influenced by the criteria used to diagnose BPD and the oxygen saturation level used to determine the supplementary oxygen requirement. Key also to interpreting lung function data in this population is whether appropriate lung function tests have been used and in an adequately sized population to make meaningful conclusions. It should also be emphasized that BPD is a poor predictor of long-term respiratory morbidity. Bearing in mind those caveats, studies have consistently demonstrated that infants who develop BPD have low compliance and functional residual capacities and raised resistances in the neonatal period. There is, however, no agreement with regard to which early lung function measurement predicts the development of BPD, likely reflecting different techniques were used in different populations in often underpowered studies. During infancy, lung function generally improves, but importantly airflow limitation persists and small airway function appears to decline. Improvements in lung function following administration of diuretics or bronchodilators have not translated into long-term improvements in respiratory outcomes. By contrast, early differences in lung function related to different ventilation modes have led to investigation and demonstration that prophylactic, neonatal high-frequency oscillation appears to protect small airway function. PMID:26131449

  6. Functional connectivity correlates of response inhibition impairment in anorexia nervosa.

    PubMed

    Collantoni, Enrico; Michelon, Silvia; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Manara, Renzo; Clementi, Maurizio; Pinato, Claudia; Forzan, Monica; Cassina, Matteo; Santonastaso, Paolo; Favaro, Angela

    2016-01-30

    Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavioral perseveration. The present study aims at exploring inhibitory control abilities and their functional connectivity correlates in patients with AN. Inhibitory control - an executive function that allows the realization of adaptive behavior according to environmental contingencies - has been assessed by means of the Stop-Signal paradigm. The study involved 155 patients with lifetime AN and 102 healthy women. A subsample underwent resting-state functional magnetic resonance imaging and was genotyped for COMT and 5-HTTLPR polymorphisms. AN patients showed an impaired response inhibition and a disruption of the functional connectivity of the ventral attention circuit, a neural network implicated in behavioral response when a stimulus occurs unexpected. The 5-HTTLPR genotype appears to significantly interact with the functional connectivity of ventral attention network in explaining task performance in both patients and controls, suggesting a role of the serotoninergic system in mechanisms of response selection. The disruption of the ventral attention network in patients with AN suggests lower efficiency of bottom-up signal filtering, which might be involved in difficulties to adapt behavioral responses to environmental needs. Our findings deserve further research to confirm their scientific and therapeutic implications. PMID:26655584

  7. Farmer's lung

    PubMed Central

    Hapke, E. J.; Seal, R. M. E.; Thomas, G. O.; Hayes, M.; Meek, J. C.

    1968-01-01

    In assessing patients suffering from farmer's lung, the acute stage must be distinguished from the chronic stage of the disease. The conspicuous radiographic signs in the acute farmer's lung episode and the often dramatic clearing make an important contribution to the diagnosis. The radiographic changes in chronic farmer's lung are not specific and cover a wide range of appearances. Even minor nodular changes are significant. Farmer's lung, acute and chronic, is not a disease predominantly characterized by a defect in gas exchange. During the acute illness the reduction in diffusing capacity is often accompanied by a decrease in lung volumes; the pulmonary function profile of the chronic stage is variable. In only a relatively small proportion of chronic farmer's lung patients does a defect in gas exchange predominate, and in some it may be manifest only during exercise. Airway obstruction is a feature of chronic farmer's lung. In chronic farmer's lung patients discrepancies between the severity of complaints and results of pulmonary function tests are not infrequent. In some patients with considerable disability conventional pulmonary function studies may demonstrate little or no impairment of the functions measured. In patients suffering from an acute farmer's lung episode, serological tests should be positive, possibly in high titre. In the chronic stage of the disease the chance of finding positive serology in a patient diminishes with the length of time elapsed since the last acute episode. The period of serological transition appears to be the third year. Images PMID:4971361

  8. Impaired cortical mitochondrial function following TBI precedes behavioral changes

    PubMed Central

    Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

    2014-01-01

    Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

  9. Impaired dendritic cell function in a spontaneous autoimmune polyneuropathy.

    PubMed

    Quan, Songhua; Kim, Hye-Jung; Dukala, Danuta; Sheng, Jian Rong; Soliven, Betty

    2015-05-01

    Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout NOD mice mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy, and is mediated by myelin protein zero (P0)-reactive Th1 cells. In this study, we focused on the effect of B7-2 deletion on the function of dendritic cells (DCs) within the context of SAP. We found that development of SAP was associated with a preponderance or increase of CD11b(+) DCs in peripheral lymph nodes and sciatic nerves. B7-2 deletion led to altered immunophenotypic properties that differ between CD11b(+) DCs and CD8α(+) DCs. Both DC subsets from B7-2 knockout NOD mice exhibited impaired capacity to capture fluorophore-labeled myelin P0, but diminished Ag-presenting function was observed only in CD11b(+) DCs. Clinical assessment, electrophysiologic studies, and splenocyte proliferation studies revealed that absence of B7-2 on DCs was sufficient to cause impaired ability to induce tolerance to P0, which could be overcome by preconditioning with IL-10. Tolerance induction by Ag-pulsed wild-type NOD DCs was dependent on IL-10 and was associated with increased CD4(+) regulatory T cells, whereas tolerance induction by IL-10-conditioned B7-2-deficient DCs was associated with increased percentages of both regulatory T cells and B10 cells in the spleen. We conclude that B7-2 deletion has an impact on the distribution of DC subsets in lymphoid organs and alters the expression of costimulatory molecules, but functional consequences are not uniform across DC subsets. Defective tolerance induction in the absence of B7-2 can be restored by preconditioning of DCs with IL-10. PMID:25825437

  10. Work related impairment of nasal function in Swedish woodwork teachers.

    PubMed Central

    Ahman, M; Holmström, M; Cynkier, I; Söderman, E

    1996-01-01

    OBJECTIVE: To study the relation between exposure and nasal function in woodwork teachers. METHODS: 39 selected woodwork teachers employed full time and 32 control subjects (other school personnel) were examined at the beginning and at the end of a working week with symptom rating, nose and throat inspection, rhinomanometry, nasal mucociliary clearance test, and a smell identification test. During one working day of the same week climate, dust and terpene concentrations were measured in all 39 schools. RESULTS: The ventilation rate was highest in rooms with mechanical ventilation. Range of total dust (personally sampled) was 0.12-1.18 mg/m3, respirable dust 0.02-0.21 mg/m3, and terpenes (area sampled) 0.02-6.8 mg/m3. In contrast to the control subjects, the woodwork teachers had more nasal symptoms on the Thursday afternoon than on the Monday morning, especially those working in rooms without mechanical ventilation. Their mucociliary clearance worsened during the week (mean increase 4 min, P < 0.001). A small impairment of olfactory function was also found, but their rhinomanometric values did not change significantly. Nasal symptoms correlated weakly with the percentage of respirable dust in the total dust. Otherwise there were no significant dose-effect relations between measured dust or terpene concentrations and nasal tests. CONCLUSIONS: The woodwork teachers had mainly reversible nasal complaints, impaired nasal mucociliary clearance and olfactory function related to the work environment, with dust concentrations below the Swedish threshold limit value of 2 mg/m3. PMID:8777447

  11. Lung function in Greenlandic and Danish children and adolescents.

    PubMed

    Krause, Tyra Grove; Pedersen, Bo V; Thomsen, Simon Francis; Koch, Anders; Wohlfahrt, Jan; Backer, Vibeke; Melbye, Mads

    2005-03-01

    Respiratory morbidity in Inuit children is high. However, little is know regarding lung function measures in this population. The forced expiratory volumes in one second (FEV(1)) and forced vital capacity (FVC) in 888 Greenlandic Inuits (N=888) and Danes (N=477) aged 6-18 years were compared. Furthermore, associations between level of lung function and atopy and lifestyle factors were estimated in Greenlanders. The effect of height on FEV(1) and FVC was significantly different in Greenlanders and Danes, this difference in lung function increased with increasing height, and could not be explained by differences in age weight and BMI. Thus, Greenlanders taller than 130 cm had up to 300-400 ml higher FEV(1) and FVC compared with Danes of the same height. Among Greenlanders, those living in settlements had the highest levels of both FEV(1) and FVC. Greenlanders had elevated levels of FEV(1) and FVC compared with Danes. The Inuit having a shorter limb length in relation to trunk height may account for these differences. However, our finding that Greenlanders living in settlements had the highest lung function level also suggests a possible role of factors in the traditional Greenlandic lifestyle. PMID:15733513

  12. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  13. Gas cooking and reduced lung function in school children

    NASA Astrophysics Data System (ADS)

    Moshammer, Hanns; Hutter, Hans-Peter; Neuberger, Manfred

    RationaleOutdoor nitrogen dioxide (NO 2) is associated with reduced respiratory health. This could be due to a unique biological effect of this gaseous pollutant or because it serves as a surrogate of fine particles from incineration sources. Cooking with gas in small kitchens produces high concentrations of gaseous irritants (mainly nitrogen dioxide), but not fine particles. ObjectivesTo study the relative impact of cooking with gas on lung function parameters in a cross sectional study of school children. MethodsNearly all elementary school children (2898 children aged 6-10 years) living in the city of Linz (capital of Upper Austria) underwent lung function testing. In a questionnaire administered simultaneously to their parents, information on household conditions including cooking and tobacco smoke exposure was collected. Impact of cooking with gas on lung function controlling for various confounders was analyzed using loglinear multiple regression. ResultsGas cooking reduced lung function parameters ranging from 1.1% (not significant) for MEF 25 up to 3.4% ( p=0.01) for peak expiratory flow (PEF). ConclusionsGas stoves can have an adverse impact on children's respiratory health. Parents and caretakers should be advised to insure good ventilation while and after cooking, especially in small and poorly ventilated rooms. This study adds to the growing evidence that gaseous pollutants from incineration sources affect respiratory health directly.

  14. Socioeconomic Status and Longitudinal Lung Function of Healthy Mexican Children

    PubMed Central

    Martínez-Briseño, David; Fernández-Plata, Rosario; Gochicoa-Rangel, Laura; Torre-Bouscoulet, Luis; Rojas-Martínez, Rosalba; Mendoza-Alvarado, Laura; García-Sancho, Cecilia; Pérez-Padilla, Rogelio

    2015-01-01

    Introduction Our aim was to estimate the longitudinal effect of Socioeconomic status (SES) on lung function growth of Mexican children and adolescents. Materials and Methods A cohort of Mexican children in third grade of primary school was followed with spirometry twice a year for 6 years through secondary school. Multilevel mixed-effects lineal models were fitted for the spirometric variables of 2,641 respiratory-healthy Mexican children. Monthly family income (in 2002 U.S. dollars [USD]) and parents’ years completed at school were used as proxies of SES. Results Individuals with higher SES tended to have greater height for age, and smaller sitting height/standing height and crude lung function. For each 1-year increase of parents’ schooling, Forced expiratory volume in 1 sec (FEV1) and Forced vital capacity (FVC) increased 8.5 (0.4%) and 10.6 mL (0.4%), respectively (p <0.05) when models were adjusted for gender. Impact of education on lung function was reduced drastically or abolished on adjusting by anthropometric variables and ozone. Conclusions Higher parental schooling and higher monthly family income were associated with higher lung function in healthy Mexican children, with the majority of the effect likely due to the increase in height-for-age. PMID:26379144

  15. Formaldehyde exposure impairs the function and differentiation of NK cells.

    PubMed

    Kim, Eun-Mi; Lee, Hwa-Youn; Lee, Eun-Hee; Lee, Ki-Mo; Park, Min; Ji, Kon-Young; Jang, Ji-Hun; Jeong, Yun-Hwa; Lee, Kwang-Ho; Yoon, Il-Joo; Kim, Su-Man; Jeong, Moon-Jin; Kim, Kwang Dong; Kang, Hyung-Sik

    2013-11-25

    We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure also induced decreases in NK cytolytic activity and in the expression of NK cell-associated genes, such as IFN-γ, perforin and CD122. To determine the effect of FA on tumorigenicity, C57BL/6 mice were subcutaneously injected with B16F10 melanoma cells after FA exposure. The mass of the B16F10 tumor and the concentration of extravascular polymorphonuclear leukocytes were greater than those in unexposed tumor-bearing control mice. The number and cytolytic activity of NK cells were also reduced in B16F10 tumor-bearing mice exposed to FA. To determine how FA reduces the NK cell number, NK precursor (pNK) cells were treated with FA, and the differentiation status of the NK cells was analyzed. NK cell differentiation was impaired by FA treatment in a concentration-dependent manner. These findings indicate that FA exposure may promote tumor progression by impairing NK cell function and differentiation. PMID:24060340

  16. Executive functioning in preschoolers with specific language impairment

    PubMed Central

    Vissers, Constance; Koolen, Sophieke; Hermans, Daan; Scheper, Annette; Knoors, Harry

    2015-01-01

    The pathogenesis of Specific Language Impairment (SLI) is still largely beyond our understanding. In this review, a neuropsychological perspective on language impairments in SLI is taken, focusing specifically on executive functioning (EF) in preschoolers (age range: 2.6–6.1 years) with SLI. Based on the studies described in this review, it can be concluded that similar to school-aged children with SLI, preschoolers with SLI show difficulties in working memory, inhibition and shifting, as revealed by both performance based measures and behavioral ratings. It seems plausible that a complex, reciprocal relationship exists between language and EF throughout development. Future research is needed to examine if, and if yes how, language and EF interact in SLI. Broad neuropsychological assessment in which both language and EF are taken into account may contribute to early detection of SLI. This in turn can lead to early and tailored treatment of children with (suspected) SLI aimed not only at stimulating language development but also at strengthening EF. PMID:26539136

  17. Thoracic dust exposure is associated with lung function decline in cement production workers.

    PubMed

    Nordby, Karl-Christian; Notø, Hilde; Eduard, Wijnand; Skogstad, Marit; Fell, Anne Kristin; Thomassen, Yngvar; Skare, Øivind; Bergamaschi, Antonio; Pietroiusti, Antonio; Abderhalden, Rolf; Kongerud, Johny; Kjuus, Helge

    2016-08-01

    We hypothesised that exposure to workplace aerosols may lead to lung function impairment among cement production workers.Our study included 4966 workers in 24 cement production plants. Based on 6111 thoracic aerosol samples and information from questionnaires we estimated arithmetic mean exposure levels by plant and job type. Dynamic lung volumes were assessed by repeated spirometry testing during a mean follow-up time of 3.5 years (range 0.7-4.6 years). The outcomes considered were yearly change of dynamic lung volumes divided by the standing height squared or percentage of predicted values. Statistical modelling was performed using mixed model regression. Individual exposure was classified into quintile levels limited at 0.09, 0.89, 1.56, 2.25, 3.36, and 14.6 mg·m(-3), using the lowest quintile as the reference. Employees that worked in administration were included as a second comparison group.Exposure was associated with a reduction in forced expiratory volume in 1 s (FEV1), forced expiratory volume in 6 s and forced vital capacity. For FEV1 % predicted a yearly excess decline of 0.84 percentage points was found in the highest exposure quintile compared with the lowest.Exposure at the higher levels found in this study may lead to a decline in dynamic lung volumes. Exposure reduction is therefore warranted. PMID:27103386

  18. Thoracic dust exposure is associated with lung function decline in cement production workers

    PubMed Central

    Notø, Hilde; Eduard, Wijnand; Skogstad, Marit; Fell, Anne Kristin; Thomassen, Yngvar; Skare, Øivind; Bergamaschi, Antonio; Pietroiusti, Antonio; Abderhalden, Rolf; Kongerud, Johny; Kjuus, Helge

    2016-01-01

    We hypothesised that exposure to workplace aerosols may lead to lung function impairment among cement production workers. Our study included 4966 workers in 24 cement production plants. Based on 6111 thoracic aerosol samples and information from questionnaires we estimated arithmetic mean exposure levels by plant and job type. Dynamic lung volumes were assessed by repeated spirometry testing during a mean follow-up time of 3.5 years (range 0.7–4.6 years). The outcomes considered were yearly change of dynamic lung volumes divided by the standing height squared or percentage of predicted values. Statistical modelling was performed using mixed model regression. Individual exposure was classified into quintile levels limited at 0.09, 0.89, 1.56, 2.25, 3.36, and 14.6 mg·m−3, using the lowest quintile as the reference. Employees that worked in administration were included as a second comparison group. Exposure was associated with a reduction in forced expiratory volume in 1 s (FEV1), forced expiratory volume in 6 s and forced vital capacity. For FEV1 % predicted a yearly excess decline of 0.84 percentage points was found in the highest exposure quintile compared with the lowest. Exposure at the higher levels found in this study may lead to a decline in dynamic lung volumes. Exposure reduction is therefore warranted. PMID:27103386

  19. Effects of nanoparticles on the mechanical functioning of the lung.

    PubMed

    Arick, Davis Q; Choi, Yun Hwa; Kim, Hyun Chang; Won, You-Yeon

    2015-11-01

    Nanotechnology is a rapidly expanding field that has very promising applications that will improve industry, medicine, and consumer products. However, despite the growing widespread use of engineered nanoparticles in these areas, very little has been done to assess the potential health risks they may pose to high-risk areas of the body, particularly the lungs. In this review we first briefly discuss the structure of the lungs and establish that the pulmonary surfactant (PS), given its vulnerability and huge contribution to healthy lung function, is a mechanism of great concern when evaluating potential nanoparticle interactions within the lung. To warrant that these interactions can occur, studies on the transport of nanoaerols are reviewed to highlight that a plethora of factors contribute to a nanoparticle's ability to travel to the deep regions of the lung where PS resides. The focus of this review is to determine the extent that physicochemical characteristics of nanoparticles such as size, hydrophobicity, and surface charge effect PS function. Numerous nanoparticle types are taken into consideration in order to effectively evaluate observed consistencies across numerous nanoparticle types and develop general trends that exist among the physicochemical characteristics of interest. Biological responses from other mechanisms/components of the lung are briefly discussed to provide further insights on how the toxicology of different nanoparticles is determined. We conclude by discussing general trends that summarize consistencies observed among the studies in regard to physicochemical properties and their effects on monolayer function, addressing current gaps in our understanding, and discussing the future outlook of this field of research. PMID:26494653

  20. Predicting ventilator-induced lung injury using a lung injury cost function.

    PubMed

    Hamlington, Katharine L; Smith, Bradford J; Allen, Gilman B; Bates, Jason H T

    2016-07-01

    Managing patients with acute respiratory distress syndrome (ARDS) requires mechanical ventilation that balances the competing goals of sustaining life while avoiding ventilator-induced lung injury (VILI). In particular, it is reasonable to suppose that for any given ARDS patient, there must exist an optimum pair of values for tidal volume (VT) and positive end-expiratory pressure (PEEP) that together minimize the risk for VILI. To find these optimum values, and thus develop a personalized approach to mechanical ventilation in ARDS, we need to be able to predict how injurious a given ventilation regimen will be in any given patient so that the minimally injurious regimen for that patient can be determined. Our goal in the present study was therefore to develop a simple computational model of the mechanical behavior of the injured lung in order to calculate potential injury cost functions to serve as predictors of VILI. We set the model parameters to represent normal, mildly injured, and severely injured lungs and estimated the amount of volutrauma and atelectrauma caused by ventilating these lungs with a range of VT and PEEP. We estimated total VILI in two ways: 1) as the sum of the contributions from volutrauma and atelectrauma and 2) as the product of their contributions. We found the product provided estimates of VILI that are more in line with our previous experimental findings. This model may thus serve as the basis for the objective choice of mechanical ventilation parameters for the injured lung. PMID:27174922

  1. X-ray findings, lung function, and respiratory symptoms in black South African vermiculite workers

    SciTech Connect

    Hessel, P.A.; Sluis-Cremer, G.K.

    1989-01-01

    Health effects have been documented among American vermiculite workers who mined and processed vermiculite contaminated with amphibole asbestos, viz., tremolite-actinolite. Workers mining and processing South Africa vermiculite (N = 172), which contains very little asbestos, underwent x-ray examination and lung function testing and completed a respiratory symptom questionnaire. The vermiculite workers were compared with other workers involved in the mining or refining of copper. Only two of the vermiculite workers showed evidence of small opacities of 1/0 or more (according to the ILO 1980 classification); lung function was comparable with the other groups of workers, and there was no excess of respiratory symptoms among the vermiculite workers. It is concluded that workers exposed to vermiculite that is minimally contaminated with asbestos are probably not at risk for pneumoconiosis, lung function impairment, or respiratory symptoms. It is likely that the health effects observed in other studies of vermiculite workers are the result of concomitant asbestos exposure. A risk of mesothelioma caused by the fiber content of the vermiculite cannot be excluded by this study.

  2. Lung Function in Sickle Cell Hemoglobinopathy Patients Compared With Healthy Subjects

    PubMed Central

    Young, Roscoe C.; Rachal, Raylinda E.; Reindorf, Carl A.; Armstrong, Earl M.; Polk, Octavius D.; Hackney, Robert L.; Scott, Roland B.

    1988-01-01

    Previous studies of lung function tests performed on patients with sickle cell disease have shown a restrictive ventilatory defect, usually a diffusion defect, and mild hypoxia at rest. The present study was undertaken to explain the pathophysiology of these changes and to extend these studies to include functional measurements not reported previously. Lung function studies were performed at rest and during treadmill walking on 66 patients with sickle cell anemia and on 16 healthy control subjects. Patients had restrictive ventilatory defects, decreased lung compliance, and uneven ventilation-perfusion ratios. These abnormalities caused an increased alveolar-arterial oxygen tension difference that caused hypoxemia. The diffusion defects were because of the sickle cell disease. Carboxyhemoglobin levels were increased in patients with sickle cell disease. This increase may be caused by a combination of factors, including increased cigarette smoking, hemolysis, and preferential survival of red blood cells that contain carbon monoxide and which do not sickle. During treadmill walking, the patients with sickle cell disease showed a decreased work tolerance caused by impaired oxygen delivery. The anaerobic threshold is reached sooner in patients with sickle cell disease and may also account for the limitations in work capacity of these patients. PMID:3418733

  3. The Role of Impaired Epidermal Barrier Function in Atopic Dermatitis.

    PubMed

    Jurakić Tončić, Ružica; Marinović, Branka

    2016-06-01

    Atopic dermatitis (AD) is a chronic, inflammatory, pruritic skin disease with increasing prevalence. The etiopathogenesis of atopic dermatitis is multifactorial and involves a complex interplay of environmental and genetic factors that induce derangements in the structure and function of the epidermal barrier and immune system. Due to great heterogeneity of etiopathogenesis, there is also great variability of clinical presentation, and diagnosis can sometimes be challenging and difficult. Diagnosis mostly relies on clinical features and laboratory tests, but morphology alone cannot reliably establish the diagnosis, so the spectrum of features associated with AD must be considered. Traditionally, patients with AD have been separated into two different subgroups, i.e. intrinsic and extrinsic. Today, most of authors prefer the outside to inside and back to outside hypothesis, suggesting that the primary disorder lies in epidermal structure and function, resulting in inflammation and immunological downstream activation which further provokes secondary barrier abnormalities. In this review, we discuss the structure and function of the epidermal barrier and the role of impaired barrier function in etiopathogenesis of atopic dermatitis. PMID:27477169

  4. Decreased function of survival motor neuron protein impairs endocytic pathways.

    PubMed

    Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S; O'Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C Q; Cook, Steven J; Poulogiannis, George; Atwood, Walter J; Hall, David H; Hart, Anne C

    2016-07-26

    Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death. PMID:27402754

  5. Violence exposure, a chronic psychosocial stressor, and childhood lung function

    PubMed Central

    Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

    2011-01-01

    Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

  6. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

    PubMed Central

    Yao, Xue; Yan, Licheng; Yao, Lin; Guan, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-01-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity. PMID:25206854

  7. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function.

    PubMed

    Yao, Xue; Yan, Licheng; Yao, Lin; Guan, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-03-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity. PMID:25206854

  8. Endothelial RIG-I activation impairs endothelial function

    SciTech Connect

    Asdonk, Tobias; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  9. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma

    SciTech Connect

    Maasilta, P. )

    1991-03-01

    Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy.

  10. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    SciTech Connect

    Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  11. Air pollution and lung function among susceptible adult subjects: a panel study

    PubMed Central

    Lagorio, Susanna; Forastiere, Francesco; Pistelli, Riccardo; Iavarone, Ivano; Michelozzi, Paola; Fano, Valeria; Marconi, Achille; Ziemacki, Giovanni; Ostro, Bart D

    2006-01-01

    Background Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. Methods Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM10–2.5) and fine (PM2.5) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and sulphur dioxide (SO2) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. Results Decrements in lung function indices (FVC and/or FEV1) associated with increasing concentrations of PM2.5, NO2 and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO2 was associated with a decrease in FEV1. No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. Conclusion This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function

  12. Effects of Lung Expansion Therapy on Lung Function in Patients with Prolonged Mechanical Ventilation

    PubMed Central

    Chen, Yen-Huey; Yeh, Ming-Chu; Hu, Han-Chung; Lee, Chung-Shu; Li, Li-Fu; Chen, Ning-Hung; Huang, Chung-Chi; Kao, Kuo-Chin

    2016-01-01

    Common complications in PMV include changes in the airway clearance mechanism, pulmonary function, and respiratory muscle strength, as well as chest radiological changes such as atelectasis. Lung expansion therapy which includes IPPB and PEEP prevents and treats pulmonary atelectasis and improves lung compliance. Our study presented that patients with PMV have improvements in lung volume and oxygenation after receiving IPPB therapy. The combination of IPPB and PEEP therapy also results in increase in respiratory muscle strength. The application of IPPB facilitates the homogeneous gas distribution in the lung and results in recruitment of collapsed alveoli. PEEP therapy may reduce risk of respiratory muscle fatigue by preventing premature airway collapse during expiration. The physiologic effects of IPPB and PEEP may result in enhancement of pulmonary function and thus increase the possibility of successful weaning from mechanical ventilator during weaning process. For patients with PMV who were under the risk of atelectasis, the application of IPPB may be considered as a supplement therapy for the enhancement of weaning outcome during their stay in the hospital.

  13. Effect of ozone exposure on lung functions and plasma prostaglandin and thromboxane concentrations in guinea pigs

    SciTech Connect

    Miller, P.D.; Ainsworth, D.; Lam, H.F.; Amdur, M.O.

    1987-03-30

    Male Hartley guinea pigs were exposed either to filtered air or to 1 ppm ozone (O/sub 3/) for 1 hr. At 2, 8, 24, or 48 hr after exposure we measured ventilation, respiratory mechanics, lung volumes, diffusing capacity for carbon monoxide (DLCO), and alveolar volume (VA) in anesthetized, tracheotomized animals. Respiratory frequency and tidal volume were unchanged in all groups. Pulmonary resistance was increased 2 hr after O/sub 3/ but returned to control at 8 hr and thereafter. Prolonged reductions in lung volumes (total lung capacity, vital capacity, functional residual capacity, and residual volume) as well as in DLCO and VA occurred after O/sub 3/, with maximum decreases at 8 and 24 hr postexposure. Increased ratios of wet lung weight to body weight were seen at 2, 8, and 24 hr. In separate groups of animals, also exposed either to filtered air or to 1 ppm O/sub 3/, plasma eicosanoid (EC) concentrations were measured at 2, 8, 24, 48, or 72 hr after exposure. Significant increases in thromboxane B2 concentrations were seen at 2, 24, and 48 hr after exposure. Plasma concentrations of 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E1 (PGE1) were increased at 24 hr and at 24, 48, and 72 hr, respectively. The nature of this long-term pulmonary response to a short-term exposure to O/sub 3/ suggests alveolar involvement, including probable alveolar duct constriction and localized pulmonary edema. Although changes in plasma EC concentrations were observed concurrent with impaired lung functions, no simple causal relationship was apparent from these studies.

  14. Hepatitis B virus antigens impair NK cell function.

    PubMed

    Yang, Yinli; Han, Qiuju; Zhang, Cai; Xiao, Min; Zhang, Jian

    2016-09-01

    An inadequate immune response of the host is thought to be a critical factor causing chronic hepatitis B virus (CHB) infection. Natural killer (NK) cells, as one of the key players in the eradication and control of viral infections, were functionally impaired in CHB patients, which might contribute to viral persistence. Here, we reported that HBV antigens HBsAg and HBeAg directly inhibited NK cell function. HBsAg and/or HBeAg blocked NK cell activation, cytokine production and cytotoxic granule release in human NK cell-line NK-92 cells, which might be related to the downregulation of activating receptors and upregulation of inhibitory receptor. Furthermore, the underlying mechanisms likely involved the suppression of STAT1, NF-κB and p38 MAPK pathways. These findings implicated that HBV antigen-mediated inhibition of NK cells might be an efficient strategy for HBV evasion, targeting the early antiviral responses mediated by NK cells and resulting in the establishment of chronic virus infection. Therefore, this study revealed the relationship between viral antigens and human immune function, especially a potential important interaction between HBV and innate immune responses. PMID:27341035

  15. Melamine Impairs Renal and Vascular Function in Rats.

    PubMed

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-01-01

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576

  16. Melamine Impairs Renal and Vascular Function in Rats

    PubMed Central

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-01-01

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576

  17. Impairment of immunological functions in genetically epilepsy-prone rats.

    PubMed

    De Sarro, G; Liberto, M C; Berlinghieri, M C; Focà, A; Aragona, M; Cavaliere, R; Gulletta, E

    1996-06-01

    1. In genetically epilepsy-prone rats (GEPR-9s), which represent a natural genetic model of epilepsy, we observed that the number of peritoneal macrophages was significantly lower with respect to normal rats, and that some functional parameters (i.e. phagocytosis and intracellular killing) of these macrophages were impaired. 2. The count of lymphocyte populations showed a predominance of T-helper over T-cytotoxic/suppressor both in the spleen and lymph nodes. Moreover, an increased T-cell/B-cell ratio was observed in GEPR-9s. Flow cytometry revealed that GEPR-9s spleens possessed a large percentage of T-helper cells in comparison to normal rats. 3. By using concanavalin A-induced proliferation of GEPR-9s cultured lymphocytes, we have shown increased functional activation. 4. We suggest that the alterations in T-cell functions in GEPR-9s could be due to the involvement of the neuroendocrine system in the modulation of immunity, in the shift between Th1 and Th2, and in the activation of stress response. PMID:8853298

  18. Neuropsychological functioning in youth with obsessive compulsive disorder: an examination of executive function and memory impairment.

    PubMed

    Lewin, Adam B; Larson, Michael J; Park, Jennifer M; McGuire, Joseph F; Murphy, Tanya K; Storch, Eric A

    2014-04-30

    Preliminary research suggests neuropsychological deficits in youth with obsessive-compulsive disorder (OCD) similar to those in adults; however, small samples and methodological confounds limit interpretation. We aimed to examine the rates and clinical correlates of cognitive sequelae in youth with OCD, focusing on executive functioning and memory abilities. Youth ages 7-17 years with OCD (N=96) completed a hypothesis-driven neuropsychological battery (including the Rey-Osterreith Complex Figure, California Verbal Learning Test, and subtests of the Delis-Kaplan Executive Function System and Wide Range Assessment of Memory and Learning) that primarily assessed executive functioning, memory and processing speed. Cognitive sequelae were identified in 65% of youth (37% using a more stringent definition of impairment). Magnitude of cognitive sequelae was not associated with OCD severity or age; however, greater neuropsychological impairments were found amongst youth prescribed atypical neuroleptics and those diagnosed with comorbid tic disorders. Comorbidity burden was associated with presence of neuropsychological impairment, but was not specific to any single test. Findings suggest that the presence of cognitive sequelae is prevalent amongst treatment-seeking youth with OCD. Deficits were found in executive functioning and non-verbal memory performance but these impairments were not associated with OCD severity. PMID:24508366

  19. Assistive Devices for Children with Functional Impairments: Impact on Child and Caregiver Function

    ERIC Educational Resources Information Center

    Henderson, Stacey; Skelton, Heather; Rosenbaum, Peter

    2008-01-01

    Functional impairments can limit a child's ability to participate in the experiences of childhood. This "deprivation" can, in turn, have a negative effect on such children's development, academic performance, and quality of life, as well as on the lives of their caregivers and families. Many adults use assistive devices to overcome functional…

  20. [Problems of lung function testing in the laboratory].

    PubMed

    Tojo, Naoko

    2006-08-01

    Spirometry is indispensable for the screening test of general respiratory function, and measurements of lung volume and diffusing capacity play an important role in the assessment of disease severity, functional disability, disease activity and response to treatment. Pulmonary function testing requires cooperation between the subjects and the examiner, and the results obtained depend on technical as well as personal factors. In order to diminish the variability of results and improve measurement accuracy, the Japan Respiratory Society published the first guidelines on the standardization of spirometry and diffusing capacity for both technical and clinical staff in 2004. It is therefore essential to distribute the guidelines to both laboratory personnel and general physicians. Furthermore, training workshops are mandatory to improve their understanding of the basics of lung function testing. Recently, there has been increasing interest in noninvasive methods of lung function testing without requiring the patient's cooperation during spontaneous breathing. Three alternative techniques, i.e. the negative expiratory pressure (NEP) method to detect expiratory flow limitation, impulse oscillation system (IOS) to measure respiratory system resistance (Rrs) and reactance (Xrs), and interruption resistance (Rint) to measure respiratory resistance have been introduced. Further study is required to determine the advantage of these methods. PMID:16989403

  1. Lung function and morphology of dogs after sublethal exposure to nitrogen dioxide

    SciTech Connect

    Johnson, W.K.; Mauderly, J.L.; Hahn, F.F.; Muggenburg, B.A.

    1982-08-01

    The relationship between respiratory function and morphological changes in 10 dogs exposed for 6 h to 69 ppm nitrogen dioxide was studied. Two additional dogs served as controls. Functional assessments included breathing pattern, breathing mechanics, forced expiration, gas exchange, and acid-base status. Gross, microscopic, and ultrastructural evaluations were made of lung tissues from dogs killed at 0.1, 1.0, 2.0, 3.0, 7.0 and 14.0 d after exposure. Functional changes were similar to those reported for man. The principal dysfunction was gas-exchange impairment, apparently resulting from foam in the airways. Breathing-pattern alterations appeared to result from stimulation of neural receptors. Gas-exchange measurements provided the most useful indicators of the pulmonary damage observed in this study.

  2. Sexual dimorphism in lung function responses to acute influenza A infection

    PubMed Central

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

  3. Restoration of alveolar type II cell function contributes to simvastatin-induced attenuation of lung ischemia-reperfusion injury.

    PubMed

    Wu, Yaqin; Lv, Junjie; Feng, Dongjie; Jiang, Feng; Fan, Xiaohu; Zhang, Zhi; Yin, Rong; Xu, Lin

    2012-12-01

    Alveolar type (AT) II cells transdifferentiate into ATI cells and as such represent a promising source for regenerating lung epithelium following lung injury. ATII cells are characterized by the presence of lamellar bodies (LBs), which store and secrete the surfactant protein-C (SP-C). Lung ischemia-reperfusion injury (LIRI) causes a distinct impairment of the ATII cell function, subsequently hindering lung repair by loss of ATI transdifferentiation. In this study, we provide new evidence that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin may restore the function of impaired ATII cells in vitro and in vivo. ATII cell lines, A549 (human) and MLE-12 (mouse), were subjected to hypoxia-reoxygenation (H/R) injury. Simvastatin pretreatment at low (5-20 µM), but not high (50-100 µM) doses markedly reduced apoptosis and increased proliferation and SP-C expression. In a rat lung ischemia-reperfusion (I/R) model, simvastatin treatment also increased ATII cell proliferation in vivo, as demonstrated by proliferating cell nuclear antigen/SP-C double staining. Transmission electron microscopy revealed that the number and volume density of LBs were significantly increased in the simvastatin-treated rat lungs. The protective effects of simvastatin were reversed in vitro by PI3-kinase (PI3K) inhibitors wortmannin and L-mevalonate, indicating that the PI3K/Akt and mevalonate pathways may be involved in simvastatin-induced ATII cell function restoration. These data demonstrate that an appropriate dose of simvastatin has a protective effect on LIRI in vitro and in vivo, due at least partially to restored ATII cell function via the HMG-CoA reductase pathway-dependent activation of PI3K/Akt signaling in a mevalonate pathway-dependent manner. PMID:23076613

  4. Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function

    PubMed Central

    2013-01-01

    Background Vitamin D is associated with lung health in epidemiologic studies, but mechanisms mediating observed associations are poorly understood. This study explores mechanisms for an effect of vitamin D in lung through an in vivo gene expression study, an expression quantitative trait loci (eQTL) analysis in lung tissue, and a population-based cohort study of sequence variants. Methods Microarray analysis investigated the association of gene expression in small airway epithelial cells with serum 25(OH)D in adult non-smokers. Sequence variants in candidate genes identified by the microarray were investigated in a lung tissue eQTL database, and also in relation to cross-sectional pulmonary function in the Health, Aging, and Body Composition (Health ABC) study, stratified by race, with replication in the Framingham Heart Study (FHS). Results 13 candidate genes had significant differences in expression by serum 25(OH)D (nominal p < 0.05), and a genome-wide significant eQTL association was detected for SGPP2. In Health ABC, SGPP2 SNPs were associated with FEV1 in both European- and African-Americans, and the gene-level association was replicated in European-American FHS participants. SNPs in 5 additional candidate genes (DAPK1, FSTL1, KAL1, KCNS3, and RSAD2) were associated with FEV1 in Health ABC participants. Conclusions SGPP2, a sphingosine-1-phosphate phosphatase, is a novel vitamin D-responsive gene associated with lung function. The identified associations will need to be followed up in further studies. PMID:24274704

  5. Recovery of impaired muscle function in severe sciatica.

    PubMed

    Balagué, F; Nordin, M; Sheikhzadeh, A; Echegoyen, A C; Skovron, M L; Bech, H; Chassot, D; Helsen, M

    2001-06-01

    were not found during the last three visits. The isokinetic tests showed a higher prevalence of muscle function impairment. At visit 5, the isokinetic test showed impaired muscle function recovery from 23% to 32%, while the manual test showed almost full recovery. The issues of agreement between manual and isokinetic muscle testing are discussed. In this selected and homogeneous cohort of patients, the prevalence of motor deficit was rather low and the outcome excellent according to the results of the manual testing. Isokinetic muscle tests showed a higher prevalence of deficit and a much slower recovery. The manual muscle test is a crude clinical test. For more indepth muscle performance evaluation, additional testing may be necessary, especially for those patients with physically demanding jobs or activities. PMID:11469737

  6. Impaired proteasome function in sporadic amyotrophic lateral sclerosis.

    PubMed

    Kabashi, Edor; Agar, Jeffrey N; Strong, Michael J; Durham, Heather D

    2012-06-01

    Abstract The ubiquitin-proteasome system, important for maintaining protein quality control, is compromised in experimental models of familial ALS. The objective of this study was to determine if proteasome function is impaired in sporadic ALS. Proteasomal activities and subunit composition were evaluated in homogenates of spinal cord samples obtained at autopsy from sporadic ALS and non-neurological control cases, compared to cerebellum as a clinically spared tissue. The level of 20S α structural proteasome subunits was assessed in motor neurons by immunohistochemistry. Catalysis of peptide substrates of the three major proteasomal activities was substantially reduced in ALS thoracic spinal cord, but not in cerebellum, accompanied by alterations in the constitutive proteasome machinery. Chymotrypsin-like activity was decreased to 60% and 65% of control in ventral and dorsal spinal cord, respectively, concomitant with reduction in the β5 subunit with this catalytic activity. Caspase- and trypsin-like activities were reduced to a similar extent (46% - 68% of control). Proteasome levels, although generally maintained, appeared reduced specifically in motor neurons by immunolabelling. In conclusion, there are commonalities of findings in sporadic ALS patients and presymptomatic SOD1-G93A transgenic mice and these implicate inadequate proteasome function in the pathogenesis of both familial and sporadic ALS. PMID:22632443

  7. Sleep Restriction Impairs Blood–Brain Barrier Function

    PubMed Central

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

    2014-01-01

    The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

  8. Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins

    PubMed Central

    Chadwick, Alexandra C.; Holme, Rebecca L.; Chen, Yiliang; Thomas, Michael J.; Sorci-Thomas, Mary G.; Silverstein, Roy L.; Pritchard, Kirkwood A.; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway. PMID:25849485

  9. Sleep restriction impairs blood-brain barrier function.

    PubMed

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

    2014-10-29

    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

  10. Immunomodulation of phloretin by impairing dendritic cell activation and function.

    PubMed

    Lin, Chi-Chen; Chu, Ching-Liang; Ng, Chin-Sheng; Lin, Ching-Yen; Chen, Der-Yuan; Pan, I-Hong; Huang, Kao-Jean

    2014-05-01

    Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-κB, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-γ production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases. PMID:24651121

  11. Improved effect of Pycnogenol on impaired spatial memory function in partial androgen deficiency rat model.

    PubMed

    Hasegawa, Noboru; Mochizuki, Miyako

    2009-06-01

    The improved effect of Pycnogenol on impaired spatial memory function was studied in orchidectomized rats. Endogenous testosterone levels were decreased by approximately one-half for 3 months after castration. In the radial arm maze, castration significantly impaired working and reference memory function without lowering motor function. Pycnogenol increased the NGF content in the hippocampus and cortex, and improved the spatial memory impairment. These observations confirmed that diagnostic accuracy can be improved by Pycnogenol in androgen-deficient rats. PMID:19142987

  12. Influence of Radiofrequency Ablation of Lung Cancer on Pulmonary Function

    SciTech Connect

    Tada, Akihiro Hiraki, Takao; Iguchi, Toshihiro; Gobara, Hideo; Mimura, Hidefumi; Toyooka, Shinichi; Kiura, Katsuyuki; Tsuda, Toshihide; Mitsuhashi, Toshiharu; Kanazawa, Susumu

    2012-08-15

    Purpose: The purpose of this study was to evaluate altered pulmonary function retrospectively after RFA. Methods: This retrospective study comprised 41 ablation sessions for 39 patients (22 men and 17 women; mean age, 64.8 years). Vital capacity (VC) and forced expiratory volume in 1 s (FEV{sub 1}) at 1 and 3 months after RFA were compared with the baseline (i.e., values before RFA). To evaluate the factors that influenced impaired pulmonary function, univariate analysis was performed by using multiple variables. If two or more variables were indicated as statistically significant by univariate analysis, these variables were subjected to multivariate analysis to identify independent factors. Results: The mean VC and FEV{sub 1} before RFA and 1 and 3 months after RFA were 3.04 and 2.24 l, 2.79 and 2.11 l, and 2.85 and 2.13 l, respectively. The values at 1 and 3 months were significantly lower than the baseline. Severe pleuritis after RFA was identified as the independent factor influencing impaired VC at 1 month (P = 0.003). For impaired FEV{sub 1} at 1 month, only severe pleuritis (P = 0.01) was statistically significant by univariate analysis. At 3 months, severe pleuritis (VC, P = 0.019; FEV{sub 1}, P = 0.003) and an ablated parenchymal volume {>=}20 cm{sup 3} (VC, P = 0.047; FEV{sub 1}, P = 0.038) were independent factors for impaired VC and FEV{sub 1}. Conclusions: Pulmonary function decreased after RFA. RFA-induced severe pleuritis and ablation of a large volume of marginal parenchyma were associated with impaired pulmonary function.

  13. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    PubMed

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

  14. Predictors of deterioration of lung function in Polish children with cystic fibrosis

    PubMed Central

    Olszowiec-Chlebna, Małgorzata; Koniarek-Maniecka, Agnieszka; Stelmach, Włodzimierz; Smejda, Katarzyna; Jerzyńska, Joanna; Majak, Paweł; Białas, Monika

    2016-01-01

    Introduction Severity of lung disease varies in patients with the same CFTR genotype. It suggests that other factors affect the severity of cystic fibrosis (CF). The aim of the study was to identify risk factors that determine lung function decline in Polish cystic fibrosis children. Material and methods The follow-up time was no less than 5 years of respiratory status observation based on the forced expiratory volume in 1 s value (FEV1). The socio-economic data, perinatal interview, presence of meconium ileus (MI), time of CF diagnosis, initiation of tobramycin inhalation solution (TIS), pancreatic function, sensitization to Aspergillus fumigatus, presence of impaired glucose tolerance (IGT) or diabetes mellitus, chronic bacterial colonization and number of exacerbations and hospitalizations were assessed. Results The mean age of 61 included children was 13.3 ±7.6 years. Delta F508 homozygosity was detected in 45.9%, 44.3% were delta F508 heterozygous, and 9.8% had other genotypes. FEV1 decline was observed among 20% of patients; the rest of the patients presented stable values of FEV1 during at least 5 years of observation. The most significant predictors related to the decline of FEV1 were presentation of MI (p = 0.0344), IGT (p = 0.0227), number of exacerbations (p = 0.0288), and early Pseudomonas aeruginosa (PA) chronic colonization (p = 0.0165) followed by late TIS initiation after the first detection of PA (p=0.0071). Neither time of diagnosis nor type of CFTR mutation was statistically significant as a predictor of lung deterioration. Conclusions The presence of MI, IGT, chronic PA colonization, and number of exacerbations are risk factors for lung function deterioration. PMID:27186187

  15. Microbubbles shunting via a patent foramen ovale impair endothelial function

    PubMed Central

    Fok, Henry; Jiang, Benyu; Chowienczyk, Phil

    2015-01-01

    Objectives Exposure to intravascular microbubbles after diving and during medical procedures alters endothelial function. The aim of this study was to investigate whether a patent foramen ovale altered forearm endothelial function by facilitating microbubbles transfer. Design Patients attended on two separate visits, at least seven days apart receiving agitated saline or no active intervention in random order. On both days, flow-mediated dilatation of the brachial artery was measured using vascular ultrasound. On the intervention visit, agitated saline was injected and the passage of microbubbles into the arterial circulation was confirmed by echocardiography. Serial flow-mediated dilatation measurements were made after agitated saline and at the same time points after no intervention. Setting St Thomas’ Hospital in London. Participants Patients with a patent foramen ovale (PFO+n = 14, 9 male, mean ± SD age 42.2 ± 10.5 years) and patients without a patent foramen ovale (PFO− n = 10, 7 male, mean ± SD age 49.4 ± 18.4 years) were recruited. Main outcome measures Change in brachial artery flow-mediated dilatation. Results In patent foramen ovale + patients, flow-mediated dilatation did not change significantly on the control day but after agitated saline reduced by 2.3 ± 0.3%, 20 minutes after bubble injection (P < 0.005 vs. corresponding change in flow-mediated dilatation during control study). There was no significant change in flow-mediated dilatation for patent foramen ovale− patients at either visit. Conclusion These results suggest that the presence of a patent foramen ovale facilitated impairment of endothelial function acutely by the transfer of microbubbles into the arterial circulation. As a patent foramen ovale is a common condition, this may be relevant to microbubbles exposure in medical procedures and in decompression illness. PMID:26668739

  16. Reconstructive procedures for impaired upper airway function: laryngeal respiration

    PubMed Central

    Müller, Andreas

    2005-01-01

    The larynx is the "bottleneck" of the human airway. For this reason, the effects of stenosing laryngeal pathologies on the vital factor respiratory gas exchange are particularly critical. Internal stabilization is a prerequisite for recovery of the laryngeal respiratory function in severe forms of inspiratory collapse (laryngomalacia). Effective laser surgery techniques have been developed to this end in recent years. Glottis-dilating surgery in cases of bilateral vocal cord motion impairment is now moving in the direction of endoscopic laser cordotomy or cordectomy, whereas arytenoidectomy and open surgical procedures are now used only rarely due to higher secondary morbidity rates. In individual cases, in particular if functional recovery is expected, temporary laterofixation of a vocal cord using an endoscopic suturing technique can be a helpful approach. Extensive laryngeal defects can be covered by means of composite grafts with mucosal lining, a supporting skeleton and their own vascularization. Autologous transplantation of the larynx, with its complex surgical and immunological problems, has become a manageable procedure. The problems of post-transplantation reinnervation and risk assessment of immunosuppression-induced recurrence of the tumor are still under consideration. Reanimation of the bilaterally paralyzed larynx by means of neurorrhaphy (neurosuture), neural grafting and, more recently, functional electrostimulation (pacemaker) represents a challenge for the coming years. In most cases of paralysis of the recurrent laryngeal nerve, a part of the muscles is maintained by synkinetic reinnervation when therapy is carried out, which however also prevents effective vocal cord movement due to simultaneous activity of agonists and antagonists. Modulation of reinnervation by means of electrostimulation and modern genetic therapy approaches justify hopes of better outcomes in the future. PMID:22073057

  17. The relation of airway size to lung function

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Sciurba, Frank C.; Fuhrman, Carl R.; Bon, Jessica M.; Park, Sang C.; Pu, Jiantao; Gur, David

    2008-03-01

    Chronic obstructive pulmonary disease may cause airway remodeling, and small airways are the mostly likely site of associated airway flow obstruction. Detecting and quantifying airways depicted on a typical computed tomography (CT) images is limited by spatial resolution. In this study, we examined the association between lung function and airway size. CT examinations and spirometry measurement of forced expiratory volume in one second as a percent predicted (FEV I%) from 240 subjects were used in this study. Airway sections depicted in axial CT section were automatically detected and quantified. Pearson correlation coefficients (PCC) were computed to compare lung function across three size categories: (1) all detected airways, (2) the smallest 50% of detected airways, and (3) the largest 50% of detected airways using the CORANOVA test. The mean number of all airways detected per subject was 117.4 (+/- 40.1) with mean size ranging from 20.2 to 50.0 mm2. The correlation between lung function (i.e., FEV I) and airway morphometry associated with airway remodeling and airflow obstruction (i.e., lumen perimeter and wall area as a percent of total airway area) was significantly stronger for smaller compared to larger airways (p < 0.05). The PCCs between FEV I and all airways, the smallest 50%, and the largest 50% were 0.583, 0.617, 0.523, respectively, for lumen perimeter and -0.560, -0.584, and -0.514, respectively, for wall area percent. In conclusion, analyzing a set of smaller airways compared to larger airways may improve detection of an association between lung function and airway morphology change.

  18. Lung function over six years among professional divers

    PubMed Central

    Skogstad, M; Thorsen, E; Haldorsen, T; Kjuus, H

    2002-01-01

    Aims: To analyse longitudinal changes in pulmonary function in professional divers and their relation with cumulative diving exposure. Methods: The study included 87 men at the start of their education as professional divers. At follow up one, three, and six years later, 83, 81, and 77 divers were reexamined. The median number of compressed air dives in the 77 divers over the follow up period was 196 (range 37–2000). A group of non-smoking policemen (n = 64) were subjected to follow up examinations in parallel with the divers. Assessment of lung function included dynamic lung volumes, maximal expiratory flow rates, and transfer factor for carbon monoxide (TlCO). The individual rates of change of the lung function variables were calculated by fitting linear regression lines to the data, expressed as percent change per year. Results: The annual reductions in forced vital capacity (FVC) and forced expired volume in one second (FEV1) were 0.91 (SD 1.22) and 0.84 (SD 1.28) per cent per year in divers, which were significantly higher than the reductions in the policemen of 0.24 (SD 1.04) and 0.16 (SD 1.07) per cent per year (p < 0.001). The annual reduction in the maximal expiratory flow rates at 25% and 75% of FVC expired (FEF25% and FEF75%) were related to the log10 transformed cumulative number of dives in a multiple regression analysis (p < 0.05). The annual reductions in TlCO were 1.33 (SD 1.85) and 0.43 (SD 1.53) per cent per year in divers and policemen (p < 0.05). Conclusions: FVC, FEV1, maximal expiratory flow rates, and TlCO were significantly reduced in divers over the follow up period when compared with policemen. The contrasts within and between groups suggest that diving has contributed to the reduction in lung function. PMID:12205238

  19. Association between lung function and airway wall density

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Fuhrman, Carl R.; Tedrow, John; Park, Sang C.; Tan, Jun; Pu, Jiantao; Drescher, John M.; Gur, David; Sciurba, Frank C.

    2009-02-01

    Computed tomography (CT) examination is often used to quantify the relation between lung function and airway remodeling in chronic obstructive pulmonary disease (COPD). In this preliminary study, we examined the association between lung function and airway wall computed attenuation ("density") in 200 COPD screening subjects. Percent predicted FVC (FVC%), percent predicted FEV1 (FEV1%), and the ratio of FEV1 to FVC as a percentage (FEV1/FVC%) were measured post-bronchodilator. The apical bronchus of the right upper lobe was manually selected from CT examinations for evaluation. Total airway area, lumen area, wall area, lumen perimeter and wall area as fraction of the total airway area were computed. Mean HU (meanHU) and maximum HU (maxHU) values were computed across pixels assigned membership in the wall and with a HU value greater than -550. The Pearson correlation coefficients (PCC) between FVC%, FEV1%, and FEV1/FVC% and meanHU were -0.221 (p = 0.002), -0.175 (p = 0.014), and -0.110 (p = 0.123), respectively. The PCCs for maxHU were only significant for FVC%. The correlations between lung function and the airway morphometry parameters were slightly stronger compared to airway wall density. MeanHU was significantly correlated with wall area (PCC = 0.720), airway area (0.498) and wall area percent (0.611). This preliminary work demonstrates that airway wall density is associated with lung function. Although the correlations in our study were weaker than a recent study, airway wall density initially appears to be an important parameter in quantitative CT analysis of COPD.

  20. Genetic Ancestry Influences Asthma Susceptibility and Lung Function Among Latinos

    PubMed Central

    Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Eng, Celeste; Nishimura, Katherine K.; Oh, Sam S.; Vora, Hita; Huntsman, Scott; Nguyen, Elizabeth A.; Hu, Donglei; Drake, Katherine A.; Conti, David V.; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Borrell, Luisa N.; Lurmann, Fred; Islam, Talat S.; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Bibbins-Domingo, Kirsten; Lenoir, Michael A.; Ford, Jean G.; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Thyne, Shannon M.; Sen, Saunak; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Williams, L. Keoki; Gilliland, Frank D.; Gauderman, W. James; Kumar, Rajesh; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. Objective To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. Methods We analyzed 5,493 Latinos with and without asthma from three independent studies. For each participant we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. Results Native American ancestry was associated with lower odds of asthma (OR=0.72, 95% confidence interval [CI]: 0.66–0.78, p=8.0×10−15), while African ancestry was associated with higher odds of asthma (OR=1.40, 95%CI: 1.14–1.72, p=0.001). These associations were robust to adjustment for covariates related to early life exposures, air pollution and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of forced expiratory volume in the first second (−77±19 ml, p=5.8×10−5 and −83±19 ml, p=1.1×10−5, respectively) and forced vital capacity (−100±21 ml, p=2.7×10−6 and −107±22 ml, p=1.0×10−6, respectively). Conclusion Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos. PMID:25301036

  1. A Function of Lung Surfactant Protein SP-B

    NASA Astrophysics Data System (ADS)

    Longo, M. L.; Bisagno, A. M.; Zasadzinski, J. A. N.; Bruni, R.; Waring, A. J.

    1993-07-01

    The primary function of lung surfactant is to form monolayers at the alveolar interface capable of lowering the normal surface tension to near zero. To accomplish this process, the surfactant must be capable of maintaining a coherent, tightly packed monolayer that avoids collapse during expiration. The positively charged amino-terminal peptide SP-B1-25 of lung surfactant-specific protein SP-B increases the collapse pressure of an important component of lung surfactant, palmitic acid (PA), to nearly 70 millinewtons per meter. This alteration of the PA isotherms removes the driving force for "squeeze-out" of the fatty acids from the primarily dipalmitoylphosphatidylcholine monolayers of lung surfactant. An uncharged mutant of SP-B1-25 induced little change in the isotherms, suggesting that a specific charge interaction between the cationic peptide and the anionic lipid is responsible for the stabilization. The effect of SP-B1-25 on fatty acid isotherms is remarkably similar to that of simple poly-cations, suggesting that such polymers might be useful as components of replacement surfactants for the treatment of respiratory distress syndrome.

  2. Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline

    PubMed Central

    Bacci, Giovanni; Paganin, Patrizia; Lopez, Loredana; Vanni, Chiara; Dalmastri, Claudia; Cantale, Cristina; Daddiego, Loretta; Perrotta, Gaetano; Dolce, Daniela; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Fiscarelli, Ersilia Vita; Taccetti, Giovanni; Lucidi, Vincenzina; Mengoni, Alessio

    2016-01-01

    Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. PMID:27355625

  3. Respiratory symptoms and lung function in animal feed workers.

    PubMed

    Jorna, T H; Borm, P J; Valks, J; Houba, R; Wouters, E F

    1994-10-01

    In a study among 194 male workers exposed to endotoxin-containing organic dust in animal feed mills, lung function was measured by flow volume curves and impedance measurements and respiratory symptoms were recorded by means of a validated questionnaire. The aims were to detect and localize airway obstruction caused by fodder dust and endotoxin, and to relate respiratory symptoms to both types of lung function measurements. Flow volume and impedance parameters were significantly related to present exposure. All impedance parameters, of the spirometric measures only FEF25, were significantly related to cumulative dust or endotoxin exposure. The changes in impedance parameters were for overall increasing resistance at 8 Hz and decreasing reactance at 8 Hz, reflecting an increase in peripheral airflow obstruction, with increasing exposure. The changes in all lung function parameters were more strongly related to (cumulative) endotoxin exposure than to inspirable dust exposure. All impedance parameters and FEV1 showed a good correlation with complaints of chronic bronchitis and breathlessness. Impedance measurement of the respiratory system proved to be a useful tool for objectively assessing (early) airflow obstruction in workers exposed to inspirable dust and endotoxin and in localizing airflow obstruction. PMID:7924472

  4. Aspects of studies on the functional impairment electrohypersensitivity

    NASA Astrophysics Data System (ADS)

    Johansson, Olle

    2010-04-01

    Persons, claiming to suffer from exposure to electromagnetic fields, have been described in the literature. In Sweden, electrohypersensitivity (EHS) is an officially fully recognized functional impairment (i.e., it is not regarded as a disease). Survey studies show that somewhere between 230,000 - 290,000 Swedish men and women - out of a population of 9,000,000 - report a variety of symptoms when being in contact with electromagnetic field (EMF) sources. Swedish electrohypersensitive people have their own handicap organization, The Swedish Association for the Electrohypersensitive, which has its own website in both Swedish and English. This organization is included in the Swedish Disability Federation (Handikappförbundens SamarbetsOrgan; HSO). One aim of our studies has been to investigate possible alterations, in the cellular and neuronal systems of these persons' skin. In summary, it is evident from our preliminary data that various alterations are present in the electrohypersensitive persons' skin that are not indicated in the skin of normal healthy volunteers.

  5. Dexamethasone impairs hypoxia-inducible factor-1 function

    SciTech Connect

    Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.

    2008-07-25

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of {alpha}- and {beta}-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1{alpha} levels in the cytosol of HepG2 cells, while nuclear HIF-1{alpha} levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients.

  6. Monocyte function is severely impaired by the fluorochrome calcein acetomethylester

    SciTech Connect

    Czepluch, Frauke S.; Olieslagers, Serve J.F.; Waltenberger, Johannes . E-mail: j.waltenberger@cardio.azm.nl

    2007-09-21

    For rapid chemotaxis quantification, cell prelabelling is often performed with the fluorochrome calcein acetomethylester (calcein AM). We investigated whether calcein AM-prelabelling is reliable for monocyte migration analysis. Human monocytes were either preexposed to calcein AM or unlabelled. Monocyte migration towards the potent chemoattractants transforming growth factor-{beta}1 (TGF-{beta}1) and N-formyl-Methionin-Leucin-Phenylalanin (fMLP) was assessed using a 48-well micro-chemotaxis chamber. For quantification, cells were visualized by light microscopy and counted. Surprisingly, random migration of calcein AM-prelabelled cells was significantly impaired compared to the unlabelled control. Accordingly, monocyte chemotaxis towards either TGF-{beta}1 or fMLP dramatically declined. Adherence of calcein AM-labelled monocytes on plastic was also significantly decreased compared to control cells. As adhesion is regarded as an essential component of monocyte migration, the reduced migration observed in calcein AM-labelled monocytes might be explained by a fluorochrome-induced adhesion defect. Therefore, use of the fluorochrome calcein AM cannot be recommended for functional testing of monocytes.

  7. Impairments of neural circuit function in Alzheimer's disease.

    PubMed

    Busche, Marc Aurel; Konnerth, Arthur

    2016-08-01

    An essential feature of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) peptides in the brain, many years to decades before the onset of overt cognitive symptoms. We suggest that during this very extended early phase of the disease, soluble Aβ oligomers and amyloid plaques alter the function of local neuronal circuits and large-scale networks by disrupting the balance of synaptic excitation and inhibition (E/I balance) in the brain. The analysis of mouse models of AD revealed that an Aβ-induced change of the E/I balance caused hyperactivity in cortical and hippocampal neurons, a breakdown of slow-wave oscillations, as well as network hypersynchrony. Remarkably, hyperactivity of hippocampal neurons precedes amyloid plaque formation, suggesting that hyperactivity is one of the earliest dysfunctions in the pathophysiological cascade initiated by abnormal Aβ accumulation. Therapeutics that correct the E/I balance in early AD may prevent neuronal dysfunction, widespread cell loss and cognitive impairments associated with later stages of the disease.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377723

  8. Unwarranted Administration of Acetylcholinesterase Inhibitors Can Impair Genioglossus and Diaphragm Muscle Function

    PubMed Central

    Eikermann, Matthias; Fassbender, Philipp; Malhotra, Atul; Takahashi, Masaya; Kubo, Shigeto; Jordan, Amy S.; Gautam, Shiva; White, David P.; Chamberlin, Nancy L.

    2012-01-01

    Background It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume. Methods The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9). Results Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram (to 70.3 = 7.6, 49.2 = 3.2, and 39.7 = 2.3% of control, respectively), decreases in diaphragm electromyogram (to 103.1 ± 6.5, 83.1 ± 4.7, and 68.7 ± 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 ± 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 ± 3% of control, whereas end-expiratory lung volume remained constant. Conclusions The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block. PMID:17893459

  9. Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage

    PubMed Central

    García-Beccaria, María; Martínez, Paula; Méndez-Pertuz, Marinela; Martínez, Sonia; Blanco-Aparicio, Carmen; Cañamero, Marta; Mulero, Francisca; Ambrogio, Chiara; Flores, Juana M; Megias, Diego; Barbacid, Mariano; Pastor, Joaquín; Blasco, Maria A

    2015-01-01

    Telomeres are considered anti-cancer targets, as telomere maintenance above a minimum length is necessary for cancer growth. Telomerase abrogation in cancer-prone mouse models, however, only decreased tumor growth after several mouse generations when telomeres reach a critically short length, and this effect was lost upon p53 mutation. Here, we address whether induction of telomere uncapping by inhibition of the TRF1 shelterin protein can effectively block cancer growth independently of telomere length. We show that genetic Trf1 ablation impairs the growth of p53-null K-RasG12V-induced lung carcinomas and increases mouse survival independently of telomere length. This is accompanied by induction of telomeric DNA damage, apoptosis, decreased proliferation, and G2 arrest. Long-term whole-body Trf1 deletion in adult mice did not impact on mouse survival and viability, although some mice showed a moderately decreased cellularity in bone marrow and blood. Importantly, inhibition of TRF1 binding to telomeres by small molecules blocks the growth of already established lung carcinomas without affecting mouse survival or tissue function. Thus, induction of acute telomere uncapping emerges as a potential new therapeutic target for lung cancer. PMID:25971796

  10. Smoking and intermediate alpha1-antitrypsin deficiency and lung function in middle-aged men.

    PubMed Central

    Larsson, C; Eriksson, S; Dirksen, H

    1977-01-01

    Lung function was evaluated in a representative population sample of 50-year-0ld men living in one Swedish city. Twenty-four smoking and 15 non-smoking men heterozygous for alpha1-antitrypsin deficiency--that is, with the protease-inhibitor (Pi1 phenotype MZ--were carefully matched for weight and smoking habit with Pi M controls. The pulmonary function of non-smoking Pi MZ subjects did not differ from that of non-smoking Pi M controls. In contrast, smoking heterozygotes showed a significant loss of elastic recoil, enlarged residual volumes, and increased closing capacity but no signs of obstructive ventilatory impairment. Most smoking Pi MZ individuals reported mild exertional dyspnoea. PMID:303135

  11. Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

    SciTech Connect

    Meng, Xue; Frey, Kirk; Matuszak, Martha; Paul, Stanton; Ten Haken, Randall; Yu, Jinming; Kong, Feng-Ming

    2014-05-01

    Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

  12. Investigations on the lung and kidney function in workers exposed to cadmium.

    PubMed Central

    Lauwerys, R R; Roels, H A; Buchet, J P; Bernard, A; Stanescu, D

    1979-01-01

    The kidney seems more sensitive to the chronic effect of cadmium than the lung. Only minor impairments of lung function (mild form of obstructive lung disease) were found after long-term occupational exposure (less than 20 yr) to moderate concentration of cadmium oxide dust and fume. This conclusion, cannot, however be extrapolated to acute or subacute inhalational exposure. The nephrotoxicity of cadmium consists in a tubular dysfunction characterized by an increased excretion of beta 2-microglobulin and giving rise to the classical tubular proteinuria and in a glomerular dysfunction evidenced by an increased excretion of high molecular weight proteins and increased levels of beta 2-microglobulin and creatinine in plasma and giving rise to a glomerular type proteinuria. These renal changes were mainly found in workers whose cadmium concentration at time of the survey exceeded 1 microgram Cd/100 ml in blood and 10 microgram Cd/g creatinine in urine. It should, however, be stressed that higher levels of Cd in blood and in urine are not necessarily associated with the presence of excessive proteinuria. In newly exposed workers, the Cd level in blood increases progressively to a plateau after several weeks. Cadmium level in urine fluctuates more. In workers exposed for several months to an airborne concentration exceeding 200 microgram/m3, Cd concentration in urine seems mainly influenced by recent exposure. Images FIGURE 1. PMID:226353

  13. Impairment of striatal mitochondrial function by acute paraquat poisoning.

    PubMed

    Czerniczyniec, Analía; Lanza, E M; Karadayian, A G; Bustamante, J; Lores-Arnaiz, S

    2015-10-01

    Mitochondria are essential for survival. Their primary function is to support aerobic respiration and to provide energy for intracellular metabolic pathways. Paraquat is a redox cycling agent capable of generating reactive oxygen species. The aim of the present study was to evaluate changes in cortical and striatal mitochondrial function in an experimental model of acute paraquat toxicity and to compare if the brain areas and the molecular mechanisms involved were similar to those observed after chronic exposure. Sprague-Dawley rats received paraquat (25 mg/Kg i.p.) or saline and were sacrificed after 24 h. Paraquat treatment decreased complex I and IV activity by 37 and 21 % respectively in striatal mitochondria. Paraquat inhibited striatal state 4 and state 3 KCN-sensitive respiration by 80 % and 62 % respectively, indicating a direct effect on respiratory chain. An increase of 2.2 fold in state 4 and 2.3 fold in state 3 in KCN-insensitive respiration was observed in striatal mitochondria from paraquat animals, suggesting that paraquat redox cycling also consumed oxygen. Paraquat treatment increased hydrogen peroxide production (150 %), TBARS production (42 %) and cardiolipin oxidation/depletion (12 %) in striatal mitochondria. Also, changes in mitochondrial polarization was induced after paraquat treatment. However, no changes were observed in any of these parameters in cortical mitochondria from paraquat treated-animals. These results suggest that paraquat treatment induced a clear striatal mitochondrial dysfunction due to both paraquat redox cycling reactions and impairment of the mitochondrial electron transport, causing oxidative damage. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics. PMID:26350412

  14. Functional Impairment in Adult Sleepwalkers: A Case-Control Study

    PubMed Central

    Lopez, Regis; Jaussent, Isabelle; Scholz, Sabine; Bayard, Sophie; Montplaisir, Jacques; Dauvilliers, Yves

    2013-01-01

    Study Objectives: To investigate the restorative quality of sleep and daytime functioning in sleepwalking adult patients in comparison with controls. Design: Prospective case-control study. Setting: Data were collected at the Sleep Disorders Center, Hôpital-Gui-de Chauliac, Montpellier, France between June 2007 and January 2011. Participants: There were 140 adult sleepwalkers (100 (median age 30 y, 55% male) in whom primary SW was diagnosed) who underwent 1 night of video polysomnography. All patients participated in a standardized clinical interview and completed a battery of questionnaires to assess clinical characteristics of parasomnia, daytime sleepiness, fatigue, insomnia, depressive and anxiety symptoms, and health-related quality of life. Results were compared with those of 100 sex- and age-matched normal controls. Interventions: N/A. Measurements and Results: Of the sleepwalkers, 22.3% presented with daily episodes and 43.5% presented with weekly episodes. Median age at sleepwalking onset was 9 y. Familial history of sleepwalking was reported in 56.6% of sleepwalkers and violent sleep related behaviors in 57.9%, including injuries requiring medical care for at least one episode in 17%. Significant associations were found between sleepwalking and daytime sleepiness, fatigue, insomnia, depressive and anxiety symptoms, and altered quality of life. Early-onset sleepwalkers had higher frequency of violent behaviors and injuries. Sleepwalkers with violent behaviors had higher frequency of sleep terrors and triggering factors, with greater alteration in health-related quality of life. Conclusion: Adult sleepwalking is a potentially serious condition that may induce violent behaviors, self-injury or injury to bed partners, sleep disruption, excessive daytime sleepiness, fatigue, and psychological distress, all of which affect health-related quality of life. Citation: Lopez R; Jaussent I; Scholz S; Bayard S; Montplaisir J; Dauvilliers Y. Functional impairment in

  15. Capture-related stressors impair immune system function in sablefish

    USGS Publications Warehouse

    Lupes, S.C.; Davis, M.W.; Olla, B.L.; Schreck, C.B.

    2006-01-01

    The sablefish Anoplopoma fimbria is a valuable North Pacific Ocean species that, when not targeted in various commercial fisheries, is often a part of discarded bycatch. Predictions of the survival of discarded fish are dependent on understanding how a fish responds to stressful conditions. Our objective was to describe the immunological health of sablefish exposed to capture stressors. In laboratory experiments designed to simulate the capture process, we subjected sablefish to various stressors that might influence survival: towing in a net, hooking, elevated seawater and air temperatures, and air exposure time. After stress was imposed, the in vitro mitogen-stimulated proliferation of sablefish leukocytes was used to evaluate the function of the immune system in an assay we validated for this species. The results demonstrated that regardless of fishing gear type, exposure to elevated seawater temperature, or time in air, the leukocytes from stressed sablefish exhibited significantly diminished proliferative responses to the T-cell mitogen, concanavalin A, or the B-cell mitogen, lipopolysaccharide. There was no difference in the immunological responses associated with seawater or air temperature. The duration and severity of the capture stressors applied in our study were harsh enough to induce significantly elevated levels of plasma cortisol and glucose, but there was no difference in the magnitude of levels among stressor treatments. These data suggest that immunological suppression occurs in sablefish subjected to capture-related stressors. The functional impairment of the immune system after capture presents a potential reason why delayed mortality is possible in discarded sablefish. Further studies are needed to determine whether delayed mortality in discarded sablefish can be caused by increased susceptibility to infectious agents resulting from stressor-mediated immunosuppression.

  16. Functional representation of olfactory impairment in early Alzheimer's disease.

    PubMed

    Förster, Stefan; Vaitl, Andreas; Teipel, Stefan J; Yakushev, Igor; Mustafa, Mona; la Fougère, Christian; Rominger, Axel; Cumming, Paul; Bartenstein, Peter; Hampel, Harald; Hummel, Thomas; Buerger, Katharina; Hundt, Walter; Steinbach, Silke

    2010-01-01

    We used [18F]fluorodeoxyglucose (FDG) PET analysis to determine performance in different olfactory domains of patients with early AD compared to cognitively healthy subjects, and to map the functional metabolic representation of olfactory impairment in the patient sample. A cohort of patients with early AD (n=24), consisting of 6 subjects with incipient AD and 18 subjects with mild AD, and a control group of 28 age-matched non-demented individuals were assembled. Patients and controls were tested for olfactory performance using the "Sniffin' Sticks" test battery [odor identification (ID), discrimination (DIS) and threshold (THR)], while patients additionally underwent resting state FDG-PET. Voxel-wise PET results in the patients were correlated with olfaction scores using the general linear model in SPM5. Patients with early AD showed significantly reduced function in all three olfactory subdomains compared to controls. After controlling for effects due to patients' age, gender, cognitive status, and treating scores in the two other olfactory subdomains as nuisance variables, ID scores correlated with normalized FDG uptake in clusters with peaks in the right superior parietal lobule, fusiform gyrus, inferior frontal gyrus, and precuneus, while DIS scores correlated with a single cluster in the left postcentral cortex, and THR scores correlated with clusters in the right thalamus and cerebellum. The subtests employed in the "Sniffin' Sticks" test battery are complementary indicators of different aspects of olfactory dysfunction in early AD, and support the theory of a parallel organized olfactory system, revealed by FDG-PET correlation analysis. PMID:20847402

  17. Impaired Error Monitoring and Correction Function in Autism

    PubMed Central

    Sokhadze, Estate; Baruth, Joshua; El-Baz, Ayman; Horrell, Timothy; Sokhadze, Guela; Carroll, Thomas; Tasman, Allan; Sears, Lonnie; Casanova, Manuel F.

    2010-01-01

    result in reduced error awareness and failure in adjustment when dealing with situations where erroneous responses may occur. This deficit might be manifested in the perseverative behaviors often seen in individuals with ASD. The results are discussed in terms of a general impairment in self-monitoring and other executive functions underlying behavioral and social disturbances in ASD. PMID:20523752

  18. GENETIC ASSOCIATION BETWEEN HUMAN CHITINASES AND LUNG FUNCTION IN COPD

    PubMed Central

    Aminuddin, F.; Akhabir, L.; Stefanowicz, D.; Paré, P.D.; Connett, J.E.; Anthonisen, N.R.; Fahy, J.V.; Seibold, M.A.; Burchard, E.G.; Eng, C.; Gulsvik, A.; Bakke, P.; Cho, M. H.; Litonjua, A.; Lomas, D.A.; Anderson, W. H.; Beaty, T.H.; Crapo, J.D.; Silverman, E.K.; Sandford, A.J.

    2013-01-01

    Two primary chitinases have been identified in humans – acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host’s immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to Chronic Obstructive Pulmonary Disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the Caucasian LHS population, the baseline forced expiratory volume in one second (FEV1) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV1 and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV1. Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups. PMID:22200767

  19. Circulating MicroRNAs: Association with Lung Function in Asthma

    PubMed Central

    Kho, Alvin T.; Sharma, Sunita; Davis, Joshua S.; Spina, Joseph; Howard, Dagnie; McEnroy, Kevin; Moore, Kip; Sylvia, Jody; Qiu, Weiliang; Weiss, Scott T.; Tantisira, Kelan G.

    2016-01-01

    Background MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated. Objective We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients. Methods We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations. Results Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development. Conclusions Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity. PMID:27362794

  20. Impairment and disability in persons with MS: do functional performance or functional limitations matter?

    PubMed

    Klaren, Rachel E; Pilutti, Lara A; Sandroff, Brian M; Motl, Robert W

    2015-01-01

    Persons with multiple sclerosis (MS) often demonstrate impairment in cardiorespiratory and musculoskeletal systems that may be associated with functional performance, functional limitations, and disability limitations. This study examined such relationships in persons with MS using Nagi's disablement model and its subsequent conceptual modifications. The sample included 63 persons with MS (75% relapsing-remitting MS, median EDSS = 4.0, and mean MS duration = 13.1 years) who underwent measurements of aerobic fitness and muscular strength (i.e. impairment), functional performance, functional limitations, and disability limitations. The data were primarily examined using path analysis in Mplus 7.0. Our final model provided an excellent fit for the data (χ² = 0.67, df = 3, p = 0.88, SRMR = 0.01, and CFI = 1.00). The final model indicated that aerobic fitness and muscular strength were indirectly associated with disability limitations in persons with MS through a pathway that included functional limitations (indirect path coefficients of 0.29 and 0.20, respectively), but not functional performance. Aerobic fitness and muscular strength may be the important targets of exercise training interventions for improving perceived functional limitations and disability limitations in persons with MS. PMID:25815752

  1. Somatic growth and lung function in sickle cell disease.

    PubMed

    Catanzaro, Tina; Koumbourlis, Anastassios C

    2014-03-01

    Somatic growth is a key indicator of overall health and well-being with important prognostic implications in the management of chronic disease. Worldwide studies of growth in children and adults with SCD have predominantly shown delayed growth (especially in terms of body weight) that is gradual and progressive in nature. However, more recent studies have shown that a substantial number of patients with SCD have normal weight gain whereas some are even obese. Height in patients with SCD is not universally affected even among those with suboptimal weight gain, whereas some achieve the same or greater height than healthy controls. The relationship between somatic growth and lung function in SCD is not yet clearly defined. As a group, patients with SCD tend to have lower lung volumes compared with healthy controls. These findings are similar across the age spectrum and across ethnic/racial lines regardless of the differences in body weight. Several mechanisms and risk factors have been proposed to explain these findings. These include malnutrition, racial differences and socioeconomic status. In addition, there are structural changes of the thorax (specifically the anterio-posterior chest diameter and anterio-posterior to lateral chest ratio) specific to sickle cell disease, that potentially interfere with normal lung growth. Although, caloric and protein intake have been shown to improve both height and weight, the composition of an optimal diet remains unclear. The following article reviews the current knowledge and controversies regarding somatic growth and its relationship with lung function in sickle cell disease (SCD) as well as the role of specific deficiencies of certain micronutrients. PMID:24268619

  2. Short-Term Effects of Fine Particulate Matter and Temperature on Lung Function among Healthy College Students in Wuhan, China.

    PubMed

    Zhang, Yunquan; He, Mingquan; Wu, Simin; Zhu, Yaohui; Wang, Suqing; Shima, Masayuki; Tamura, Kenji; Ma, Lu

    2015-07-01

    Ambient fine particulate matter (PM) has been associated with impaired lung function, but the effect of temperature on lung function and the potential interaction effect between PM and temperature remain uncertain. To estimate the short-term effects of PM2.5 combined with temperature on lung function, we measured the daily peak expiratory flow (PEF) in a panel of 37 healthy college students in four different seasons. Meanwhile, we also monitored daily concentrations of indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm), ambient temperature and relative humidity of the study area, where the study participants lived and attended school. Associations of air pollutants and temperature with lung function were assessed by generalized estimating equations (GEEs). A 10 μg/m3 increase of indoor PM2.5 was associated with a change of -2.09 L/min in evening PEF (95%CI: -3.73 L/min--0.51 L/min) after adjusting for season, height, gender, temperature and relative humidity. The changes of -2.17 L/min (95%CI: -3.81 L/min- -0.52 L/min) and -2.18 L/min (95%CI: -3.96 L/min--0.41 L/min) in evening PEF were also observed after adjusting for outdoor SO2 and NO2 measured by Environmental Monitoring Center 3 kilometers away, respectively. An increase in ambient temperature was found to be associated with a decrease in lung function and our results revealed a small but significant antagonistic interactive effect between PM2.5 and temperature. Our findings suggest that ambient PM2.5 has an acute adverse effect on lung function in young healthy adults, and that temperature also plays an important role. PMID:26184254

  3. Effects of Functional Impairment on Internalizing Symptom Trajectories in Adolescence: A Longitudinal, Growth Curve Modelling Study

    ERIC Educational Resources Information Center

    Cleverley, Kristin; Bennett, Kathryn; Duku, Eric

    2013-01-01

    Despite the fact that psychosocial and functional impairment has long been acknowledged as an important aspect of psychiatric diagnosis and treatment, relatively little is known about the longitudinal relationship between psychiatric symptoms and functional impairment. This is particularly true in childhood and adolescence. Understanding how…

  4. Obesity's Effects on the Onset of Functional Impairment among Older Adults

    ERIC Educational Resources Information Center

    Jenkins, Kristi Rahrig

    2004-01-01

    Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

  5. Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

    PubMed Central

    Lee, Meng-Rui; Yang, Ching-Yao; Chang, Kai-Ping; Keng, Li-Ta; Yen, David Hung-Tsang; Wang, Jann-Yuan; Wu, Huey-Dong; Lee, Li-Na; Yu, Chong-Jen

    2013-01-01

    Background There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature. Methods Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months. Results Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062). Conclusions NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors. PMID:23483998

  6. Lung Function Measurements in Rodents in Safety Pharmacology Studies

    PubMed Central

    Hoymann, Heinz Gerd

    2012-01-01

    The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies. PMID:22973226

  7. Functional imaging of the lungs with gas agents.

    PubMed

    Kruger, Stanley J; Nagle, Scott K; Couch, Marcus J; Ohno, Yoshiharu; Albert, Mitchell; Fain, Sean B

    2016-02-01

    This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children. PMID:26218920

  8. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    PubMed Central

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  9. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome.

    PubMed

    Uriarte, Juan J; Meirelles, Thayna; Gorbenko Del Blanco, Darya; Nonaka, Paula N; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  10. Self-reported physical activity and lung function two months after cardiac surgery – a prospective cohort study

    PubMed Central

    2014-01-01

    Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691

  11. Women with TSC: Relationship between Clinical, Lung Function and Radiological Features in a Genotyped Population Investigated for Lymphangioleiomyomatosis

    PubMed Central

    Imeri, Gianluca; Palumbo, Giuseppina; La Briola, Francesca; Tresoldi, Silvia; Volpi, Angela; Gualandri, Lorenzo; Ghelma, Filippo; Alfano, Rosa Maria; Montanari, Emanuele; Gorio, Alfredo; Lesma, Elena; Peron, Angela; Canevini, Maria Paola; Centanni, Stefano

    2016-01-01

    The advent of pharmacological therapies for lymphangioleiomyomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by chest computer tomography (CT) should not be underestimated. We retrospectively investigated, in a cohort of TSC outpatients of San Paolo Hospital (Milan, Italy) 1) the role of pulmonary function tests (PFTs) for LAM diagnosis, 2) the association between LAM and other features of TSC (e.g. demography, extrapulmonary manifestations, genetic mutations, etc.), and 3) the characteristics of patients with multifocal micronodular pneumocyte hyperplasia (MMPH). Eighty-six women underwent chest CT scan; pulmonary involvement was found in 66 patients (77%; 49% LAM with or without MMPH, and 28% MMPH alone). LAM patients were older, with a higher rate of pneumothorax, presented more frequently with renal and hepatic angiomyolipomas, and tended to have a TSC2 mutation profile. PFTs, assessed in 64% of women unaffected by cognitive impairments, revealed a lower lung diffusion capacity in LAM patients. In multivariate analysis, age, but not PFTs, resulted independently associated with LAM diagnosis. Patients with MMPH alone did not show specific clinical, functional or genetic features. A mild respiratory impairment was most common in LAM-TSC patients: In conclusions, PFTs, even if indicated to assess impairment in lung function, are feasible in a limited number of patients, and are not significantly useful for LAM diagnosis in women with TSC. PMID:27171001

  12. Pulmonary Function Testing After Stereotactic Body Radiotherapy to the Lung

    SciTech Connect

    Bishawi, Muath; Kim, Bong; Moore, William H.; Bilfinger, Thomas V.

    2012-01-01

    Purpose: Surgical resection remains the standard of care for operable early-stage non-small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. Methods and Materials: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]% {<=}50% predicted, FEV%/forced vital capacity [FVC]% {<=}70%). Changes in tumor volume were also assessed by computed tomography. Results: Of a total of 30 patients with Stage I and II lung cancer, there were 7 patients in the COPD group (4 men, 3 women), and 23 in t he No-COPD group (9 men, 14 women). At a mean follow-up time of 4 months, for the COPD and No-COPD patients, pretreatment and posttreatment FEV% was similar: 39 {+-} 5 vs. 40 {+-} 9 (p = 0.4) and 77 {+-} 0.5 vs. 73 {+-} 24 (p = 0.9), respectively. The diffusing capacity of the lungs for carbon monoxide (DL{sub CO}) did significantly increase for the No-COPD group after SBRT treatment: 60 {+-} 24 vs. 69 {+-} 22 (p = 0.022); however, DL{sub CO} was unchanged for the COPD group: 49 {+-} 13 vs. 50 {+-} 14 (p = 0.8). Although pretreatment tumor volume was comparable for both groups, tumor volume significantly shrank in the No-COPD group from 19 {+-} 24 to 9 {+-} 16 (p < 0.001), and there was a trend in the COPD patients from 12 {+-} 9 to 6 {+-} 5 (p = 0.06). Conclusion: SBRT did not seem to have an effect on FEV{sub 1} and FVC, but it shrank tumor volume and

  13. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function.

    PubMed

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F; Nielsen, Michael B; Mortensen, Jann

    2012-06-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD

  14. Increased Risk of Wheeze and Decreased Lung Function after Respiratory Syncytial Virus Infection

    PubMed Central

    Zomer-Kooijker, Kim; van der Ent, Cornelis K.; Ermers, Marieke J. J.; Uiterwaal, Cuno S. P. M.; Rovers, Maroeska M.; Bont, Louis J.

    2014-01-01

    Background A relationship between hospitalization for respiratory syncytial virus (RSV) bronchiolitis and asthma development has been suggested in case-control studies. Objective The aim of this study was to assess the risk of current wheeze, asthma, and lung function at school age in infants previously hospitalized for RSV bronchiolitis compared to non-hospitalized children. Methods For this study, data from a prospective birth cohort of unselected, term-born infants (n = 553), of whom 4 (0.7%) were hospitalized for RSV bronchiolitis, and a prospective patient cohort of 155 term infants hospitalized for RSV bronchiolitis were used. Respiratory outcomes at age 6 in children hospitalized for RSV bronchiolitis were compared to non-hospitalized children. Results The risk of current wheeze was higher in hospitalized patients (n = 159) compared to non-hospitalized children (n = 549) (adjusted odds ratio (OR) 3.2 (95% CI 1.2–8.1). Similarly, the risk of current asthma, defined as a doctor’s diagnosis of asthma plus current symptoms or medication use, was higher in hospitalized patients (adjusted OR 3.1 (95% CI 1.3–7.5). Compared to non-hospitalized children, RSV bronchiolitis hospitalization was associated with lower lung function (mean difference FEV1% predicted −6.8 l (95% CI (−10.2 to −3.4). Conclusions and Clinical Relevance This is the first study showing that hospitalization for RSV bronchiolitis during infancy is associated with increased risk of wheezing, current asthma, and impaired lung function as compared to an unselected birth cohort at age 6. PMID:24498037

  15. A systematic review of the association between pleural plaques and changes in lung function

    PubMed Central

    Kopylev, Leonid; Christensen, Krista Yorita; Brown, James S; Cooper, Glinda S

    2015-01-01

    Objectives To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations. Methods Database searches of PubMed and Web of Science were supplemented by review of papers’ reference lists and journals’ tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥two reviewers. Meta-analyses of 20 studies estimated a summary effect of the decrements in per cent predicted (%pred) forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) associated with presence of pleural plaques. Results Among asbestos-exposed workers, the presence of pleural plaques was associated with statistically significant decrements in FVC (4.09%pred, 95% CI 2.31 to 5.86) and FEV1 (1.99%pred, 95% CI 0.22 to 3.77). Effects of similar magnitude were seen when stratifying by imaging type (X-ray or high-resolution CT) and when excluding studies with potential methodological limitations. Undetected asbestosis was considered as an unlikely explanation of the observed decrements. Several studies provided evidence of an association between size of pleural plaques and degree of pulmonary decrease, and presence of pleural plaques and increased rate or degree of pulmonary impairment. Conclusions The presence of pleural plaques is associated with a small, but statistically significant mean difference in FVC and FEV1 in comparison to asbestos-exposed individuals without plaques or other abnormalities. From a public health perspective, small group mean decrements in lung function coupled with an increased rate of decline in lung function of the exposed population may be consequential. PMID:25504898

  16. Displacement as a predictor of functional impairment in tsunami-exposed children.

    PubMed

    Lee, Christopher; Du, Ye Beverly; Christina, Desy; Palfrey, Judith; O'Rourke, Edward; Belfer, Myron

    2015-01-01

    Thirty months after the Indian Ocean tsunami of 26 December 2004, thousands of families in Aceh Province, Indonesia, remained in temporary barracks while sanitation conditions and non-governmental organisation support deteriorated. This study sought to determine the factors associated with functional impairment in a sample of 138 displaced and non-displaced Acehnese children. Using multivariate linear regression models, it was found that displacement distance was a consistent predictor of impairment using the Brief Impairment Scale. Exposure to tsunami-related trauma markers was not significantly linked with impairment in the model. Paternal employment was a consistent protective factor for child functioning. These findings suggest that post-disaster displacement and the subsequent familial economic disruption are significant predictors of impaired functioning in children's daily activities. Post-disaster interventions should consider the disruption of familiar environments for families and children when relocating vulnerable populations to avoid deleterious impacts on children's functioning. PMID:25231556

  17. Cognitive and motor function of neurologically impaired extremely low birth weight children

    PubMed Central

    Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen

    2015-01-01

    BACKGROUND: Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. OBJECTIVE: To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). METHODS: Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. RESULTS: Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). CONCLUSION: Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed. PMID:26435676

  18. Tigecycline targets nonsmall cell lung cancer through inhibition of mitochondrial function.

    PubMed

    Jia, Xuefeng; Gu, Zhenfang; Chen, Wenming; Jiao, Junbo

    2016-08-01

    Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains therapeutically a challenge. A strategy to target NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. We show that tigecycline, an FDA-approved antibiotic drug, preferentially targets NSCLC cells. Tigecycline is effective in inhibiting proliferation and inducing apoptosis of multiple cell lines derived from two common NSCLC subtypes: adenocarcinoma and squamous cell carcinoma. Tigecycline also dose-dependently inhibits colony formation of NSCLC subpopulation of cells with highly proliferative and invasive properties. Compared to NSCLC cells, tigecycline affects proliferation and survival of normal fibroblast cells significantly to a less extent. More importantly, tigecycline significantly inhibits NSCLC tumor growth through decreasing proliferation and increasing apoptosis of tumor cells in vivo. Tigecycline significantly inhibits mitochondrial respiration, mitochondrial membrane potential, and ATP levels and increases reactive oxygen species (ROS), suggesting that tigecycline impairs mitochondrial functions. Our study suggests that tigecycline may be a useful therapeutic agent, and inhibiting mitochondrial functions may represent a new targeted therapy for NSCLC. PMID:27009695

  19. Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking

    PubMed Central

    Stoleski, Saso; Minov, Jordan; Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka

    2015-01-01

    INTRODUCTION: Job exposure in agricultural workers often leads to respiratory impairment. AIM: To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. METHODS: A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. RESULTS: The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. CONCLUSION: The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways.

  20. Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression.

    PubMed

    Yong, Kol Jia; Basseres, Daniela S; Welner, Robert S; Zhang, Wen Cai; Yang, Henry; Yan, Benedict; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Battelli, Chiara; Hetherington, Christopher J; Ye, Min; Zhang, Hong; Maroni, Giorgia; O'Brien, Karen; Magli, Maria Cristina; Borczuk, Alain C; Varticovski, Lyuba; Kocher, Olivier; Zhang, Pu; Moon, Young-Choon; Sydorenko, Nadiya; Cao, Liangxian; Davis, Thomas W; Thakkar, Bhavin M; Soo, Ross A; Iwama, Atsushi; Lim, Bing; Halmos, Balazs; Neuberg, Donna; Tenen, Daniel G; Levantini, Elena

    2016-08-01

    Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBPα (CCAAT/enhancer binding protein α) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBPα suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBPα expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBPα expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBPα deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBPα-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBPα is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBPα loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBPα and high BMI1. PMID:27488898

  1. Effect of Five Genetic Variants Associated with Lung Function on the Risk of Chronic Obstructive Lung Disease, and Their Joint Effects on Lung Function

    PubMed Central

    Soler Artigas, María; Wain, Louise V.; Repapi, Emmanouela; Obeidat, Ma'en; Sayers, Ian; Burton, Paul R.; Johnson, Toby; Zhao, Jing Hua; Albrecht, Eva; Dominiczak, Anna F.; Kerr, Shona M.; Smith, Blair H.; Cadby, Gemma; Hui, Jennie; Palmer, Lyle J.; Hingorani, Aroon D.; Wannamethee, S. Goya; Whincup, Peter H.; Ebrahim, Shah; Smith, George Davey; Barroso, Inês; Loos, Ruth J. F.; Wareham, Nicholas J.; Cooper, Cyrus; Dennison, Elaine; Shaheen, Seif O.; Liu, Jason Z.; Marchini, Jonathan; Dahgam, Santosh; Naluai, Åsa Torinsson; Olin, Anna-Carin; Karrasch, Stefan; Heinrich, Joachim; Schulz, Holger; McKeever, Tricia M.; Pavord, Ian D.; Heliövaara, Markku; Ripatti, Samuli; Surakka, Ida; Blakey, John D.; Kähönen, Mika; Britton, John R.; Nyberg, Fredrik; Holloway, John W.; Lawlor, Debbie A.; Morris, Richard W.; James, Alan L.; Jackson, Cathy M.; Hall, Ian P.

    2011-01-01

    Rationale: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied. Objectives: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP. Methods: By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. Measurements and Main Results: Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10–12 risk alleles was associated with a reduction in FEV1 (β = –72.21 ml, P = 3.90 × 10−4) and FEV1/FVC (β = –1.53%, P = 6.35 × 10−6), and with COPD (odds ratio = 1.63, P = 1.46 × 10−5). Conclusions: Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score. PMID:21965014

  2. The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function

    PubMed Central

    Overgaard, Christian E.; Schlingmann, Barbara; Dorsainvil White, StevenClaude; Ward, Christina; Fan, Xian; Swarnakar, Snehasikta; Brown, Lou Ann S.; Guidot, David M.

    2015-01-01

    Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions (“spikes”) containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS. PMID:25888574

  3. The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function.

    PubMed

    Overgaard, Christian E; Schlingmann, Barbara; Dorsainvil White, StevenClaude; Ward, Christina; Fan, Xian; Swarnakar, Snehasikta; Brown, Lou Ann S; Guidot, David M; Koval, Michael

    2015-06-15

    Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS. PMID:25888574

  4. Clinical Assessment of Functional Movement in Adults with Visual Impairments

    ERIC Educational Resources Information Center

    Ray, Christopher T.; Horvat, Michael; Williams, Michael; Blasch, Bruce B.

    2007-01-01

    Adults with visual impairments have significantly more health risks than do sighted adults because of a number of factors, including the lower mineral density of their femoral neck bones, which is indicative of reduced weight-bearing exercise; their lesser maximal strength; and their higher rates of stroke, osteoporosis, depression, hypertension,…

  5. Pulmonary function impairment in patients with combined pulmonary fibrosis and emphysema with and without airflow obstruction

    PubMed Central

    Kitaguchi, Yoshiaki; Fujimoto, Keisaku; Hanaoka, Masayuki; Honda, Takayuki; Hotta, Junichi; Hirayama, Jiro

    2014-01-01

    Background The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis. We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction. Subjects and methods Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a β2-agonist) as follows: CPFE patients with airflow obstruction (CPFE OB+ group, n=11), and CPFE patients without airflow obstruction (CPFE OB− group, n=20). Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD) patients (n=49). Results In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB− group than in the CPFE OB+ and COPD groups. In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB− group than in the CPFE OB+ group. In pulmonary function, lung hyperinflation was not apparent in the CPFE OB− group. Impairment of diffusion capacity was severe in both the CPFE OB− and CPFE OB+ groups. Impulse oscillometry showed that respiratory resistance was not apparent in the CPFE OB− group compared with the COPD group, and that easy collapsibility of small airways during expiration of tidal breath was not apparent in the CPFE OB+ group compared with the COPD group. Dynamic hyperinflation following metronome-paced incremental hyperventilation was significantly greater in the COPD group than in the CPFE OB− group, and also tended to be greater in the CPFE OB+ group than

  6. Natural variability of lung function in young healthy school children.

    PubMed

    Kirkby, Jane; Bountziouka, Vassiliki; Lum, Sooky; Wade, Angie; Stocks, Janet

    2016-08-01

    Knowledge about long-term variability of lung function in healthy children is essential when monitoring and treating those with respiratory disease over time. The aim of this study was to define the natural variability in spirometry in young children after an interval of 12 months.The Size and Lung function In Children study was a prospective study designed to assess spirometry and body size, shape and composition in a multi-ethnic population of London school children. 14 schools with a wide range of socioeconomic circumstances were recruited. Spirometric and anthropometric assessments and parental questionnaires pertaining to respiratory symptoms, previous medical history, pubertal status and socioeconomic circumstances were completed at baseline and ∼1 year later.Technically acceptable spirometry data on two occasions ∼1 year apart (range 9-16 months) were available in 758 children (39% boys, mean±sd age 8.1±1.6 years), 593 of whom were classified as "healthy". Mean±sd within-subject between-test variability was 0.05±0.6 z-scores, with 95% of all the children achieving a between-test variability within ±1.2 z-scores (equating to ∼13% predicted).Natural variations of up to 1.2 z-scores occur in healthy children over ∼1 year. These must be considered when interpreting results from annual reviews in those with lung disease who are otherwise stable, if unnecessary further investigations or changes in treatment are to be avoided. PMID:27076582

  7. Delayed Liver Function Impairment Secondary to Interferon β-1a Use in Multiple Sclerosis

    PubMed Central

    Liao, Ming-Feng; Yen, Su-Chen; Chun-Yen, Lin; Rong-Kuo, Lyu

    2013-01-01

    Interferon β-1a is a widely used immunomodulation treatment for multiple sclerosis. Liver function impairment is a common side effect and usually develops in the first 6 months after interferon use. Here, we describe 2 multiple sclerosis patients who developed delayed liver function impairment 5 years after receiving interferon β-1a treatment. Their liver function recovered after discontinuing interferon use, and further detailed hepatological evaluations excluded other etiologies of liver function impairment. Our case reports illustrate that liver function impairment induced by interferon β-1a can be delayed for 5 years after starting treatment and, probably, this is an idiosyncratic reaction. Regular liver function monitoring in multiple sclerosis patients who receive interferon β is necessary even after the first 6 months of treatment, especially in those patients with concomitant use of other liver-toxic medications. PMID:23904853

  8. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    PubMed

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P < 0.05). In situ hybridization and immunofluorescence identified PEDF production primarily in alveolar epithelium. Hyperoxia reduced alveolarization in WT mice (P < 0.05) but not in PEDF(-/-) mice. WT hyperoxic mice had fewer platelet endothelial cell adhesion molecule (PECAM)-positive cells per alveolus (1.4 ± 0.4) than RA-exposed mice (4.3 ± 0.3; P < 0.05); this reduction was absent in hyperoxic PEDF(-/-) mice. The interactive regulation of lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors. PMID:25054647

  9. Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans

    PubMed Central

    Thum, Thomas; Schmitter, Kerstin; Fleissner, Felix; Wiebking, Volker; Dietrich, Bernd; Widder, Julian D.; Jazbutyte, Virginija; Hahner, Stefanie; Ertl, Georg; Bauersachs, Johann

    2011-01-01

    Aims Hyperaldosteronism is associated with vascular injury and increased cardiovascular events. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular homeostasis. We hypothesized that hyperaldosteronism impairs EPC function and vascularization capacity in mice and humans. Methods and results We characterized the effects of aldosterone and mineralocorticoid receptor (MR) blockade on EPC number and function as well as vascularization capacity and endothelial function. Treatment of human EPC with aldosterone induced translocation of the MR and impaired multiple cellular functions of EPC, such as differentiation, migration, and proliferation in vitro. Impaired EPC function was rescued by pharmacological blockade or genetic ablation of the MR. Aldosterone protein kinase A (PKA) dependently increased reactive oxygen species formation in EPC. Aldosterone infusion in mice impaired EPC function, EPC homing to vascular structures and vascularization capacity in a MR-dependent but blood pressure-independent manner. Endothelial progenitor cells from patients with primary hyperaldosteronism compared with controls of similar age displayed reduced migratory potential. Impaired EPC function was associated with endothelial dysfunction. MR blockade in patients with hyperaldosteronism improved EPC function and arterial stiffness. Conclusion Endothelial progenitor cells express a MR that mediates functional impairment by PKA-dependent increase of reactive oxygen species. Normalization of EPC function may represent a novel mechanism contributing to the beneficial effects of MR blockade in cardiovascular disease prevention and treatment. PMID:20926363

  10. Accuracy of forced oscillation technique to assess lung function in geriatric COPD population

    PubMed Central

    Tse, Hoi Nam; Tseng, Cee Zhung Steven; Wong, King Ying; Yee, Kwok Sang; Ng, Lai Yun

    2016-01-01

    Introduction Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population. Aims To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients. Study design A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812. Methods Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. “Resistance” and “reactance” FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation. Results In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4–0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07–0.49 vs 0.61–0.67), small airway (r=0.05–0.48 vs 0.56–0.65), and lung volume (r=0.12–0.29 vs 0.43–0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not. Conclusion FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance

  11. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation.

    PubMed

    Moeller, Alexander; Carlsen, Kai-Hakon; Sly, Peter D; Baraldi, Eugenio; Piacentini, Giorgio; Pavord, Ian; Lex, Christiane; Saglani, Sejal

    2015-06-01

    This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases. PMID:26028633

  12. The Association Between Urinary Phthalates and Lung Function

    PubMed Central

    Cakmak, Sabit; Hebbern, Chris; Saravanabhavan, Gurusankar

    2014-01-01

    Objective: To investigate the influence of phthalate exposure on lung function in the Canadian population. Methods: We tested the association between 1-second forced expiratory volume (FEVl), forced vital capacity (FVC), and urinary phthalate metabolite levels in a nationally representative sample of 3147, from 6 to 49 years old. Results: An interquartile increase in mono-n-butyl phthalate was associated with decreases in percent predicted FEV1 of 0.8% (95% confidence interval = 0.3 to 1.4) and in FVC of 0.9% (95% confidence interval = 0.3 to 1.5). Results were similar for mono-3-carboxypropyl phthalate, mono-benzyl phthalate, and di(2-ethylhexyl) phthalate metabolites, but significant effects of the latter were only seen in males and those at least 17 years old. Conclusions: These results provide evidence that phthalate exposure may adversely affect lung function in the Canadian population. Given that these chemicals are ubiquitous, the population health burden may be significant if the associations were causal. PMID:24709763

  13. Parent and Self-Ratings of Executive Function in Adolescents with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hughes, Deanna M.; Turkstra, Lyn S.; Wulfeck, Beverly B.

    2009-01-01

    Background: There is accumulating evidence that adolescents with specific language impairment (SLI) have impairments in domains beyond formal language that may affect academic and social outcomes. The findings of previous studies as well as parent reports of behavioural concerns suggest that they lag behind peers in functions such as…

  14. Distinct Patterns of Brain Function in Children with Isolated Spelling Impairment: New Insights

    ERIC Educational Resources Information Center

    Gebauer, Daniela; Enzinger, Christian; Kronbichler, Martin; Schurz, Matthias; Reishofer, Gernot; Koschutnig, Karl; Kargl, Reinhard; Purgstaller, Christian; Fazekas, Franz; Fink, Andreas

    2012-01-01

    Studies investigating reading and spelling difficulties heavily focused on the neural correlates of reading impairments, whereas spelling impairments have been largely neglected so far. Hence, the aim of the present study was to investigate brain structure and function of children with isolated spelling difficulties. Therefore, 31 children, aged…

  15. Impaired Executive Functions in Subjects with Frequent Nightmares as Reflected by Performance in Different Neuropsychological Tasks

    ERIC Educational Resources Information Center

    Simor, Peter; Pajkossy, Peter; Horvath, Klara; Bodizs, Robert

    2012-01-01

    Nightmare disorder is a prevalent parasomnia characterized by vivid and highly unpleasant dream experiences during night time sleep. The neural background of disturbed dreaming was proposed to be associated with impaired prefrontal and fronto-limbic functioning during REM sleep. We hypothesized that the impaired prefrontal and fronto-limbic…

  16. IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function.

    PubMed

    Park, Jung-Bum; Nagar, Harsha; Choi, Sujeong; Jung, Saet-Byel; Kim, Hyun-Woo; Kang, Shin Kwang; Lee, Jun Wan; Lee, Jin Hyup; Park, Jeen-Woo; Irani, Kaikobad; Jeon, Byeong Hwa; Song, Hee-Jung; Kim, Cuk-Seong

    2016-05-01

    Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and cancer cells. However, the function of IDH2 in vascular endothelial cells is mostly unknown. In this study the effects of IDH2 deficiency on mitochondrial and vascular function were investigated in endothelial cells. IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial-specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown-induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function. PMID:26898144

  17. Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury.

    PubMed

    Shults, Jill A; Curtis, Brenda J; Chen, Michael M; O'Halloran, Eileen B; Ramirez, Luis; Kovacs, Elizabeth J

    2015-11-01

    Clinical data indicate that cutaneous burn injuries covering greater than 10% of the total body surface area are associated with significant morbidity and mortality, in which pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxicated at the time of hospital admission, which increases days on ventilators by 3-fold, and doubles the length of hospitalization, compared to non-intoxicated burn patients. The most common drinking pattern in the United States is binge drinking, where an individual rapidly consumes alcoholic beverages (4 for women, 5 for men) in 2 h. An estimated 38 million Americans binge drink, often several times per month. Experimental data demonstrate that a single binge-ethanol exposure, prior to scald injury, impairs innate and adaptive immune responses, thereby enhancing infection susceptibility and amplifying pulmonary inflammation, neutrophil infiltration, and edema, and is associated with increased mortality. Since these characteristics are similar to those observed in ARDS burn patients, our study objective was to determine whether ethanol intoxication and burn injury and the subsequent pulmonary congestion affect physiological parameters of lung function, using non-invasive and unrestrained plethysmography in a murine model system. Furthermore, to mirror young adult binge-drinking patterns, and to determine the effect of multiple ethanol exposures on pulmonary inflammation, we utilized an episodic binge-ethanol exposure regimen, where mice were exposed to ethanol for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. Our analyses demonstrate mice exposed to episodic binge ethanol and burn injury have higher mortality, increased pulmonary congestion and neutrophil infiltration, elevated neutrophil chemoattractants, and respiratory dysfunction, compared to burn or ethanol intoxication alone

  18. Impaired functional differentiation for categories of objects in the ventral visual stream: A case of developmental visual impairment.

    PubMed

    Martinaud, Olivier; Pouliquen, Dorothée; Parain, Dominique; Goldenberg, Alice; Gérardin, Emmanuel; Hannequin, Didier; Altarelli, Irène; Ramus, Franck; Hertz-Pannier, Lucie; Dehaene-Lambertz, Ghislaine; Cohen, Laurent

    2015-10-01

    We report the case of a 14-year-old girl suffering from severe developmental visual impairment along with delayed language and cognitive development, and featuring a clear-cut dissociation between spared dorsal and impaired ventral visual pathways. Visual recognition of objects, including faces and printed words, was affected. In contrast, movement perception and visually guided motor control were preserved. Structural MRI was normal on inspection, but Voxel Based Morphometry (VBM) revealed reduced grey matter density in the mesial occipital and ventral occipito-temporal cortex. Functional MRI during the perception of line drawings uncovered impaired differentiation which is normally observed at even younger ages: no local category preferences could be identified within the occipito-temporal cortex for faces, houses, words or tools. In contrast, movement-related activations appeared to be normal. Finally, those abnormalities evolved on the background of chronic bilateral occipital epileptic activity, including continuous spike-wave discharges during sleep, which may be considered as the primary cause of non-specific intellectual disability and visual impairment. PMID:26272240

  19. Recovery from silver-nanoparticle-exposure-induced lung inflammation and lung function changes in Sprague Dawley rats.

    PubMed

    Song, Kyung Seuk; Sung, Jae Hyuck; Ji, Jun Ho; Lee, Ji Hyun; Lee, Jong Seong; Ryu, Hyeon Ryol; Lee, Jin Kyu; Chung, Yong Hyun; Park, Hyun Min; Shin, Beom Soo; Chang, Hee Kyung; Kelman, Bruce; Yu, Il Je

    2013-03-01

    In a previous study, the lung function, as indicated by the tidal volume, minute volume, and peak inspiration flow, decreased during 90 days of exposure to silver nanoparticles and was accompanied by inflammatory lesions in the lung morphology. Therefore, this study investigated the recovery from such lung function changes in rats following the cessation of 12 weeks of nanoparticle exposure. Male and female rats were exposed to silver nanoparticles (14-15 nm diameter) at concentrations of 0.66 × 10(6) particles/cm(3) (49 μg/m(3), low dose), 1.41 × 10(6) particles/cm(3) (117 μg/m(3), middle dose), and 3.24 × 10(6) particles/cm(3) (381 μg/m(3), high dose) for 6 h/day in an inhalation chamber for 12 weeks. The rats were then allowed to recover. The lung function was measured every week during the exposure period and after the cessation of exposure, plus animals were sacrificed after the 12-week exposure period, and 4 weeks and 12 weeks after the exposure cessation. An exposure-related lung function decrease was measured in the male rats after the 12-week exposure period and 12 weeks after the exposure cessation. In contrast, the female rats did not show a consistent lung function decrease either during the exposure period or following the exposure cessation. The histopathology showed a gradual recovery from the lung inflammation in the female rats, whereas the male rats in the high-dose group exhibited persistent inflammation throughout the 12-week recovery period. Therefore, the present results suggest a potential persistence of lung function changes and inflammation induced by silver nanoparticle exposure above the no observed adverse effect level. PMID:22264098

  20. Maternal high-fat diet is associated with impaired fetal lung development.

    PubMed

    Mayor, Reina S; Finch, Katelyn E; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D; Frank, Aaron P; Hahner, Lisa D; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F; Rosenfeld, Charles R; Savani, Rashmin C; Clegg, Deborah J

    2015-08-15

    Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

  1. Image-based modeling of lung structure and function

    PubMed Central

    Tawhai, Merryn H.; Lin, Ching-Long

    2010-01-01

    Current state-of-the-art in image-based modeling allows derivation of patient-specific models of the lung, lobes, airways, and pulmonary vascular trees. The application of traditional engineering analyses of fluid and structural mechanics to image-based subject-specific models has the potential to provide new insight into structure-function relationships in the individual via functional interpretation that complements imaging and experimental studies. Three major issues that are encountered in studies of air flow through the bronchial airways are the representation of airway geometry, the imposition of physiological boundary conditions, and the treatment of turbulence. Here we review some efforts to resolve each of these issues, with particular focus on image-based models that have been developed to simulate air flow from the mouth to the terminal bronchiole, and subjected to physiologically meaningful boundary conditions via image registration and soft tissue mechanics models. PMID:21105146

  2. Musical tasks targeting preserved and impaired functions in two dementias

    PubMed Central

    Halpern, Andrea R; Golden, Hannah L; Magdalinou, Nadia; Witoonpanich, Pirada; Warren, Jason D

    2015-01-01

    Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer's disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial. PMID:25773640

  3. Musical tasks targeting preserved and impaired functions in two dementias.

    PubMed

    Halpern, Andrea R; Golden, Hannah L; Magdalinou, Nadia; Witoonpanich, Pirada; Warren, Jason D

    2015-03-01

    Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer's disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial. PMID:25773640

  4. Brain Injury Impairs Working Memory and Prefrontal Circuit Function

    PubMed Central

    Smith, Colin J.; Xiong, Guoxiang; Elkind, Jaclynn A.; Putnam, Brendan; Cohen, Akiva S.

    2015-01-01

    More than 2.5 million Americans suffer a traumatic brain injury (TBI) each year. Even mild to moderate TBI causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI), the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice, while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI. PMID:26617569

  5. Recycling Energy to Restore Impaired Ankle Function during Human Walking

    PubMed Central

    Collins, Steven H.; Kuo, Arthur D.

    2010-01-01

    Background Humans normally dissipate significant energy during walking, largely at the transitions between steps. The ankle then acts to restore energy during push-off, which may be the reason that ankle impairment nearly always leads to poorer walking economy. The replacement of lost energy is necessary for steady gait, in which mechanical energy is constant on average, external dissipation is negligible, and no net work is performed over a stride. However, dissipation and replacement by muscles might not be necessary if energy were instead captured and reused by an assistive device. Methodology/Principal Findings We developed a microprocessor-controlled artificial foot that captures some of the energy that is normally dissipated by the leg and “recycles” it as positive ankle work. In tests on subjects walking with an artificially-impaired ankle, a conventional prosthesis reduced ankle push-off work and increased net metabolic energy expenditure by 23% compared to normal walking. Energy recycling restored ankle push-off to normal and reduced the net metabolic energy penalty to 14%. Conclusions/Significance These results suggest that reduced ankle push-off contributes to the increased metabolic energy expenditure accompanying ankle impairments, and demonstrate that energy recycling can be used to reduce such cost. PMID:20174659

  6. SU-E-J-86: Lobar Lung Function Quantification by PET Galligas and CT Ventilation Imaging in Lung Cancer Patients

    SciTech Connect

    Eslick, E; Kipritidis, J; Keall, P; Bailey, D; Bailey, E

    2014-06-01

    Purpose: The purpose of this study was to quantify the lobar lung function using the novel PET Galligas ([68Ga]-carbon nanoparticle) ventilation imaging and the investigational CT ventilation imaging in lung cancer patients pre-treatment. Methods: We present results on our first three lung cancer patients (2 male, mean age 78 years) as part of an ongoing ethics approved study. For each patient a PET Galligas ventilation (PET-V) image and a pair of breath hold CT images (end-exhale and end-inhale tidal volumes) were acquired using a Siemens Biograph PET CT. CT-ventilation (CT-V) images were created from the pair of CT images using deformable image registration (DIR) algorithms and the Hounsfield Unit (HU) ventilation metric. A comparison of ventilation quantification from each modality was done on the lobar level and the voxel level. A Bland-Altman plot was used to assess the difference in mean percentage contribution of each lobe to the total lung function between the two modalities. For each patient, a voxel-wise Spearmans correlation was calculated for the whole lungs between the two modalities. Results: The Bland-Altman plot demonstrated strong agreement between PET-V and CT-V for assessment of lobar function (r=0.99, p<0.001; range mean difference: −5.5 to 3.0). The correlation between PET-V and CT-V at the voxel level was moderate(r=0.60, p<0.001). Conclusion: This preliminary study on the three patients data sets demonstrated strong agreement between PET and CT ventilation imaging for the assessment of pre-treatment lung function at the lobar level. Agreement was only moderate at the level of voxel correlations. These results indicate that CT ventilation imaging has potential for assessing pre-treatment lobar lung function in lung cancer patients.

  7. Short- and Mid-Term Changes in Lung Function after Bilateral Pulmonary Metastasectomy.

    PubMed

    Welter, Stefan; Cheufou, Danjouma; Zahin, Mahmood; Kampe, Sandra; Darwiche, Kaid; Weinreich, Gerhard; Stamatis, Georgios

    2016-03-01

    Introduction The resection of pulmonary metastases is associated with a loss of lung function. The amount of functional impairment after bilateral metastasectomy remains unclear. Because only around 35% of those patients may expect long-term survival, it is important to preserve enough pulmonary function for an adequate quality of life. This analysis of 31 bilaterally operated patients was performed to describe the amount of pulmonary function loss. Methods This is a post-hoc subanalysis and comparison of a population that was published before. All pulmonary metastasectomies were performed through an anteroaxillary thoracotomy in all patients. Resections were performed with staplers, electrocautery, or laser. All patients had pulmonary function tests (PFTs) preoperative and after 3 months at the follow-up visit, including spirometry, diffusing capacity of lung for carbon monoxide (Dlco) and blood gases. Of the 31 bilaterally operated cases, 15 had additional PFTs after each staged operation before discharge from hospital. Results Altogether, 271 nodules (median 7, mean 8.2) were removed from the 31 patients with a lobectomy in 2, a segmentectomy in 8, and multiple wedge resections in 21 patients, with this being the largest resection. The mean loss of pulmonary function at follow-up visit was forced vital capacity (FVC) - 15.2%, total lung capacity (TLC) - 13.8%, forced expiratory volume in 1 second (FEV1) - 16.3%, and Dlco - 10.3%, all of which were significant (p = < 0.001). The 15 patients with PFTs after each operation showed a stepwise decrease of volume parameters and Dlco with deepest values after the second surgery of around - -40% from preoperative values. At this time, Po 2 was also significantly reduced by 10 mm Hg (p = 0.01). Comparing the bilateral group with 86 patients after unilateral metastasectomy, we found significantly more nodules removed in the bilateral group (8.2 vs. 3.1; p < 0.001) and that the loss

  8. Is the doctor hostile? obstructive impairments and the hostility rule in federal black lung claims

    SciTech Connect

    Cogan, T.F.

    1995-11-01

    There is little doubt that an Administrative Law Judge may discount the opinion of a doctor as hostile if that doctor renders an opinion that is contrary to something fundamental to the Act, whether that fundamental aspect be contained in the regulations or in the Act itself. Among those things fundamental to the Act is that legal Coal Workers Pneumoconiosis manifests itself in many kinds of impairments, including obstructive impairments and those restrictive. What is less clear, however, is whether an ALJ must reject an opinion where the expert testifies that CWP cannot cause obstructive impairments. It is the position of this article that ALJ has a duty to reject such an opinion, either in its entirety, if the dogma infects all of the doctor`s opinions, or so much of those opinions as are infected.

  9. Comorbidity between reading disability and math disability: Concurrent psychopathology, functional impairment, and neuropsychological functioning

    PubMed Central

    Willcutt, Erik G.; Petrill, Stephen A.; Wu, Sarah; Boada, Richard; DeFries, John C.; Olson, Richard K.; Pennington, Bruce F.

    2013-01-01

    Reading disability (RD) and Math Disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), RD+MD (N = 188), and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and ten neuropsychological processes. Groups with RD only, MD only, and RD+MD were significantly impaired versus the control group on nearly all measures, and the group with RD+MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and seven of ten neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD, and suggest that RD and MD are distinct but related disorders that co-occur due to shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension. PMID:23449727

  10. Characterization of mitochondrial function in cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function.

    PubMed

    Atlante, Anna; Favia, Maria; Bobba, Antonella; Guerra, Lorenzo; Casavola, Valeria; Reshkin, Stephan Joel

    2016-06-01

    Evidence supporting the occurrence of oxidative stress in Cystic Fibrosis (CF) is well established and the literature suggests that oxidative stress is inseparably linked to mitochondrial dysfunction. Here, we have characterized mitochondrial function, in particular as it regards the steps of oxidative phosphorylation and ROS production, in airway cells either homozygous for the F508del-CFTR allele or stably expressing wt-CFTR. We find that oxygen consumption, ΔΨ generation, adenine nucleotide translocator-dependent ADP/ATP exchange and both mitochondrial Complex I and IV activities are impaired in CF cells, while both mitochondrial ROS production and membrane lipid peroxidation increase. Importantly, treatment of CF cells with the small molecules VX-809 and 4,6,4'-trimethylangelicin, which act as "correctors" for F508del CFTR by rescuing the F508del CFTR-dependent chloride secretion, while having no effect per sè on mitochondrial function in wt-CFTR cells, significantly improved all the above mitochondrial parameters towards values found in the airway cells expressing wt-CFTR. This novel study on mitochondrial bioenergetics provides a springboard for future research to further understand the molecular mechanisms responsible for the involvement of mitochondria in CF and identify the proteins primarily responsible for the F508del-CFTR-dependent mitochondrial impairment and thus reveal potential novel targets for CF therapy. PMID:27146408

  11. Comorbidity between reading disability and math disability: concurrent psychopathology, functional impairment, and neuropsychological functioning.

    PubMed

    Willcutt, Erik G; Petrill, Stephen A; Wu, Sarah; Boada, Richard; Defries, John C; Olson, Richard K; Pennington, Bruce F

    2013-01-01

    Reading disability (RD) and math disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), and RD + MD (N = 188) and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and 10 neuropsychological processes. Groups with RD only, MD only, and RD + MD were significantly impaired versus the control group on nearly all measures, and the group with RD + MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and 7 of 10 neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD and suggest that RD and MD are distinct but related disorders that co-occur because of shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension. PMID:23449727

  12. The Health-Impaired Miner Under the Black Lung Legislation. Revised.

    ERIC Educational Resources Information Center

    Clague, Ewan; And Others

    The report reviews the administration of the Federal Coal Mine Health and Safety Act of 1969 with respect to coal workers' pneumoconiosis (black Lung) and analyzes the results. The objective of establishing and maintaining cleaner air in the mines has been substantially achieved by the Bureau of Mines inspection system. The second, which provided…

  13. Lung function in retired coke oven plant workers.

    PubMed Central

    Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

    1992-01-01

    Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

  14. Lung function measurement with multiple-breath-helium washout system.

    PubMed

    Wang, J-Y; Suddards, M E; Mellor, C J; Owers-Bradley, J R

    2013-04-01

    Multiple-breath-washout (MBW) measurements are regarded as a sensitive technique which can reflect the ventilation inhomogeneity of respiratory airways. Typically nitrogen is used as the tracer gas and is washed out by pure oxygen in multiple-breath-nitrogen washout (MBNW) tests. In this study, instead of using nitrogen, (4)He is used as the tracer gas with smaller gas density which may be able to reach deeper into our lungs in a given time and the helium washout results may be more sensitive to the ventilation inhomogeneity in small airways. A multiple-breath-helium-washout (MBHW) system developed for the lung function study is also presented. Quartz tuning forks with a resonance frequency of 32,768Hz have been used for detecting the change of the respiratory gas density. The resonance frequency of the quartz tuning fork decreases linearly with increasing density of the surrounding gas. Knowing the CO2 concentration from the infrared carbon dioxide detector, the helium concentration can be determined. Results from 14 volunteers (3 mild asthmatics, 4 tobacco smokers, 1 with asthma history, 1 with COPD history, 5 normal) have shown that mild asthmatics have higher ventilation inhomogeneity in either conducting or acinar airways (or both). A feature has been found in washout curve of single breaths from 4 tobacco smokers with different length of smoking history which may indicate the early stage of respiratory ventilation inhomogeneity in acinar airways. PMID:22835436

  15. Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights.

    PubMed

    Frerichs, I; Dudykevych, T; Hinz, J; Bodenstein, M; Hahn, G; Hellige, G

    2001-07-01

    Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity. PMID:11408411

  16. Quantification of heterogeneity in lung disease with image-based pulmonary function testing

    PubMed Central

    Stahr, Charlene S.; Samarage, Chaminda R.; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S.; Zosky, Graeme; Boucher, Richard C.; Siu, Karen K. W.; Mall, Marcus A.; Parsons, David W.; Dubsky, Stephen; Fouras, Andreas

    2016-01-01

    Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool. PMID:27461961

  17. Quantification of heterogeneity in lung disease with image-based pulmonary function testing.

    PubMed

    Stahr, Charlene S; Samarage, Chaminda R; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S; Zosky, Graeme; Boucher, Richard C; Siu, Karen K W; Mall, Marcus A; Parsons, David W; Dubsky, Stephen; Fouras, Andreas

    2016-01-01

    Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool. PMID:27461961

  18. Pilates Method for Lung Function and Functional Capacity in Obese Adults.

    PubMed

    Niehues, Janaina Rocha; Gonzáles, Inês; Lemos, Robson Rodrigues; Haas, Patrícia

    2015-01-01

    Obesity is defined as the condition in which the body mass index (BMI) is ≥ 30 kg/m2 and is responsible for decreased quality of life and functional limitations. The harmful effects on ventilatory function include reduced lung capacity and volume; diaphragmatic muscle weakness; decreased lung compliance and stiffness; and weakness of the abdominal muscles, among others. Pilates is a method of resistance training that works with low-impact muscle exercises and is based on isometric exercises. The current article is a review of the literature that aims to investigate the hypothesis that the Pilates method, as a complementary method of training, might be beneficial to pulmonary function and functional capacity in obese adults. The intent of the review was to evaluate the use of Pilates as an innovative intervention in the respiratory dysfunctions of obese adults. In studies with other populations, it has been observed that Pilates can be effective in improving chest capacity and expansion and lung volume. That finding is due to the fact that Pilates works through the center of force, made ​​up of the abdominal muscles and gluteus muscles lumbar, which are responsible for the stabilization of the static and dynamic body that is associated with breath control. It has been observed that different Pilates exercises increase the activation and recruitment of the abdominal muscles. Those muscles are important in respiration, both in expiration and inspiration, through the facilitation of diaphragmatic action. In that way, strengthening the abdominal muscles can help improve respiratory function, leading to improvements in lung volume and capacity. The results found in the current literature review support the authors' observations that Pilates promotes the strengthening of the abdominal muscles and that improvements in diaphragmatic function may result in positive outcomes in respiratory function, thereby improving functional capacity. However, the authors did not

  19. Visual impairment, visual functioning, and quality of life assessments in patients with glaucoma.

    PubMed Central

    Parrish, R K

    1996-01-01

    BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage. PMID:8981717

  20. Preserved otolith organ function in caspase-3 deficient mice with impaired horizontal semicircular canal function

    PubMed Central

    Armstrong, Patrick A; Wood, Scott J; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko

    2015-01-01

    Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: 1) horizontal angular vestibular-ocular reflex (hVOR) to evaluate semicircular canal function, and 2) otolith-ocular reflex (OOR) to evaluate otolith organ function, and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo-off vertical axis rotation (pOVAR) to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow phase eye velocity (HEV) and vertical eye position (VEP) was evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 −/− mice had severely impaired hVOR gain, while Casp3 +/− mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low to mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function. PMID:25827332

  1. Echocardiographic evaluation of pulmonary venous blood flow and cardiac function changes during one-lung ventilation

    PubMed Central

    Lee, Su Hyun; Kim, Namo; Kim, Hyun IL; Oh, Young Jun

    2015-01-01

    Objectives: The intra-pulmonary shunt induced by one-lung ventilation (OLV), is alleviated by increased pulmonary blood flow by gravitational redistribution and hypoxic pulmonary vasoconstriction. We investigated the changes of pulmonary venous blood flow (PVBF) and biventricular function during OLV with echocardiography. And the correlation between PVBF and intra-pulmonary shunt fraction (Qs/Qt) was evaluated. Methods: PVBF of the left upper pulmonary vein and cardiac function were measured with echocardiography in twenty-five patients who underwent elective thoracic surgery in left lateral decubitus. Qs/Qt and PaO2 were measured with blood gas analysis. Data was obtained at 10 min after two-lung ventilation in supine (TLV-S) and lateral decubitus position (TLV-L), and at 10, 20 and 30 min after OLV in lateral decubitus position (OLV-10, -20 and -30). Results: There were significant changes in PVBF among TLV-S, TLV-L and OLV-10 (959.5±280.8, 1416.9±489.7 and 1999.9±670.5 ml/min; P<0.05, respectively). There were not differences in PVBF, Qs/Qt and PaO2 among OLV-10, -20 and -30. There were an inverse correlation between percent change of PVBF and change of Qs/Qt (r2 = 0.5; P<0.0001) and positive correlations between the percent change of PVBF and change of PaO2 (r2 = 0.4; P<0.0001) during OLV over TLV-L. No significant changes in biventricular systolic and diastolic function were observed during positional change and OLV. Conclusions: A remarkable change of PVBF relevant to gravitational distribution and hypoxic pulmonary vasoconstriction was proved by echocardiography. And PVBF changes could represent the changes of Qs/Qt and PaO2 during OLV. However, biventricular function was not impaired during OLV. PMID:26550232

  2. The effect of negative affect on cognition: Anxiety, not anger, impairs executive function.

    PubMed

    Shields, Grant S; Moons, Wesley G; Tewell, Carl A; Yonelinas, Andrew P

    2016-09-01

    It is often assumed that negative affect impairs the executive functions that underlie our ability to control and focus our thoughts. However, support for this claim has been mixed. Recent work has suggested that different negative affective states like anxiety and anger may reflect physiologically separable states with distinct effects on cognition. However, the effects of these 2 affective states on executive function have never been assessed. As such, we induced anxiety or anger in participants and examined the effects on executive function. We found that anger did not impair executive function relative to a neutral mood, whereas anxiety did. In addition, self-reports of induced anxiety, but not anger, predicted impairments in executive function. These results support functional models of affect and cognition, and highlight the need to consider differences between anxiety and anger when investigating the influence of negative affect on fundamental cognitive processes such as memory and executive function. (PsycINFO Database Record PMID:27100367

  3. Effects of laparoscopic cholecystectomy on lung function: A systematic review

    PubMed Central

    Bablekos, George D; Michaelides, Stylianos A; Analitis, Antonis; Charalabopoulos, Konstantinos A

    2014-01-01

    AIM: To present and integrate findings of studies investigating the effects of laparoscopic cholecystectomy on various aspects of lung function. METHODS: We extensively reviewed literature of the past 24 years concerning the effects of laparoscopic cholecystectomy in comparison to the open procedure on many aspects of lung function including spirometric values, arterial blood gases, respiratory muscle performance and aspects of breathing control, by critically analyzing physiopathologic interpretations and clinically important conclusions. A total of thirty-four articles were used to extract information for the meta-analysis concerning the impact of the laparoscopic procedure on lung function and respiratory physiopathology. The quality of the literature reviewed was evaluated by the number of their citations and the total impact factor of the corresponding journals. A fixed and random effect meta-analysis was used to estimate the pooled standardized mean difference of studied parameters for laparoscopic (LC) and open (OC) procedures. A crude comparison of the two methods using all available information was performed testing the postoperative values expressed as percentages of the preoperative ones using the Mann-Whitney two-sample test. RESULTS: Most of the relevant studies have investigated and compared changes in spirometric parameters.The median percentage and interquartile range (IQR) of preoperative values in forced vital capacity (FVC), forced expiratory volume in 1 s and forced expiratory flow (FEF) at 25%-75% of FVC (FEF25%-75%) expressed as percentage of their preoperative values 24 h after LC and OC were respectively as follows: [77.6 (73.0, 80.0) L vs 55.4 (50.0, 64.0) L, P < 0.001; 76.0 (72.3, 81.0) L vs 52.5 (50.0, 56.7) L, P < 0.001; and 78.8 (68.8, 80.9) L/s vs 60.0 (36.1, 66.1) L/s, P = 0.005]. Concerning arterial blood gases, partial pressure of oxygen [PaO2 (kPa)] at 24 or 48 h after surgical treatment showed reductions that were significantly

  4. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    PubMed Central

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%–55% of levomilnacipran ER–treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial

  5. Cognitive and functional impairment in Chinese elderly with late-onset depression.

    PubMed

    Tam, C W C; Lam, L C W

    2012-03-01

    OBJECTIVES. To investigate cognitive and functional impairment in Chinese elderly subjects with late-onset depression. METHODS. Subjects with late-onset depression and who were clinically non-demented were recruited. Their cognitive and functional scores were compared with those of cognitively normal elderly controls and elderly persons with mild cognitive impairment. Functional ability was assessed by the Disability Assessment for Dementia score. Various cognitive domains were assessed including global cognitive function, delayed episodic memory, working memory, and categorical verbal fluency test. RESULTS. A total of 105 depressed subjects and 324 non-depressed controls (149 normal elderly controls and 175 with mild cognitive impairment) were recruited. The depression group had significantly poorer performance in all cognitive assessments compared to the normal elderly control group. The depression group had a similar cognitive profile to those with mild cognitive impairment, except that its subjects had slightly better performance in the Categorical Verbal Fluency Test, delayed recall testing, and the Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive subscale test. Depressed subjects had significantly lower functional scores in instrumental activities of daily living than the non-depressed, normal elderly controls, and those with mild cognitive impairment. CONCLUSIONS. Our results demonstrate that Chinese elderly with late-onset depression had cognitive impairments in multiple domains similar to those encountered in the age- and sex-matched non-depressed controls with mild cognitive impairment. However, their functional performance was significantly poorer than that in these controls. This study provided extensive characterisation of the range and depth of cognitive and functional impairments in elderly patients with late-onset depression. PMID:22447802

  6. Exploring Heart and Lung Function in Space: ARMS Experiments

    NASA Technical Reports Server (NTRS)

    Kuipers, Andre; Cork, Michael; LeGouic, Marine

    2002-01-01

    The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long

  7. Pulmonary physiology: future directions for lung function testing in COPD.

    PubMed

    Brusasco, Vito; Barisione, Giovanni; Crimi, Emanuele

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a term that encompasses different pathological conditions having excessive airflow limitation in common. A wide body of knowledge has been accumulated over the last century explaining the mechanisms by which airway (chronic bronchitis) and parenchymal (emphysema) diseases lead to an indistinguishable spirometric abnormality. Although the definition of emphysema is anatomical, early studies showed that its presence can be inferred with good approximation from measurements of lung mechanics and gas exchange, in addition to simple spirometry. Studies using tests of ventilation distribution showed that abnormalities are present in smokers with normal spirometry, although these tests were not predictive of development of COPD. At the beginning of the third millennium, new documents and guidelines for diagnosis and treatment of COPD were developed, in which the functional diagnosis of COPD was restricted, for the sake of simplicity, to simple spirometry. In recent years, there has been a resurgence of interest in separating bronchitic from emphysematous phenotype of COPD. For this purpose, high-resolution computed tomography scanning has been added to diagnostic work-up. At the same time, methods for lung function testing have been refined and seem promising for detection of early small airways abnormalities. Among them are the forced oscillation technique and the nitrogen phase III slope analysis of the multiple-breath washout test, which may provide information on ventilation inhomogeneity. Moreover, the combined assessment of diffusing capacity for nitric oxide and carbon monoxide may be more sensitive than the latter alone for partitioning diffusive components at parenchymal level. PMID:25257934

  8. Truncation of the Catalytic Domain of the Cylindromatosis Tumor Suppressor Impairs Lung Maturation1

    PubMed Central

    Trompouki, Eirini; Tsagaratou, Ageliki; Kosmidis, Stylianos K; Dollé, Pascal; Qian, Jun; Kontoyiannis, Dimitris L; Cardoso, Wellington V; Mosialos, George

    2009-01-01

    Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor κB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 (CyldΔ9/Δ9 mice) using a conditional approach. Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. In accordance with previous studies, fibroblasts from CyldΔ9/Δ9 embryos had hyperactive nuclear factor κB and c-Jun kinase pathways compared with control fibroblasts. CyldΔ9/Δ9 newborn mice were smaller than wild-type littermates with a short and kinky tail and nomajor developmental defects. However, CyldΔ9/Δ9 mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 CyldΔ9/Δ9 lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle. and endothelial structures. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. PMID:19412431

  9. ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

    PubMed Central

    Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

    2012-01-01

    The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

  10. Anxiety symptoms and functional impairment: A systematic review of the correlation between the two measures.

    PubMed

    McKnight, Patrick E; Monfort, Samuel S; Kashdan, Todd B; Blalock, Dan V; Calton, Jenna M

    2016-04-01

    Researchers and clinicians assume a strong, positive correlation between anxiety symptoms and functional impairment. That assumption may be well-justified since diagnostic criteria typically include functional impairment. Still, the relationship remains largely unavailable in any systematic review. Our aim with this paper was to provide empirical evidence for this assumed relationship and to document the observed correlations between anxiety symptom measures and functional impairment measures. Correlations existed for symptoms of six anxiety disorders (Panic Disorder, Agoraphobia, Social Anxiety Disorder, Post-Traumatic Stress Disorder, Generalized Anxiety Disorder, Obsessive Compulsive Disorder) across four functional domains (global, social, occupational, and physical). Overall, the mean of 497 correlations across all disorders and functional domains was modest (r=.34); since the variability between disorders and functional domains tended to be rather large, we explored these correlations further. We presented these results and the potential explanations for unexpected findings along with the clinical and research implications. PMID:26953005

  11. Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Wanke, T.; Merkle, M.; Formanek, D.; Zifko, U.; Wieselthaler, G.; Zwick, H.; Klepetko, W.; Burghuber, O. C.

    1994-01-01

    BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients

  12. The aftermath of terrorism: posttraumatic stress and functional impairment after the 2011 Oslo bombing

    PubMed Central

    Solberg, Øivind; Blix, Ines; Heir, Trond

    2015-01-01

    Objective: In the present study we wanted to investigate the link between exposure, posttraumatic stress symptomatology, and functional impairment in the aftermath of terrorism. Method: Posttraumatic stress symptomatology and functional impairment related to the Oslo bombing 22nd of July, 2011, in directly and indirectly exposed individuals (N = 1927) were assessed together with demographics, exposure, peri-traumatic reactions, and event centrality approximately 1 year after the attack. Results: Directly and indirectly exposed individuals qualifying for posttraumatic stress disorder (PTSD) reported similar peri-traumatic reactions, event centrality, and functional impairment. However, clusters within the PTSD symptomatology were differentially associated with impairment as a function of their exposure. In the directly exposed group, all clusters within the PTSD symptomatology were associated with impairment in function, while only emotional numbing was associated with impairment within the indirectly exposed group. Conclusion: Considering that terror attacks frequently involve directly exposed individuals and a larger population of indirectly exposed individuals, this finding is of importance, especially in the design of intervention programs and the development of treatment policies. PMID:26300833

  13. Investigating performance and lung function in a hot, humid and ozone-polluted environment.

    PubMed

    Gomes, Elisa Couto; Stone, Vicki; Florida-James, Geraint

    2010-09-01

    Large urbanized areas, where sports events take place, have a polluted environment and can also reach high temperatures and humidity levels. The aim of this study was to investigate the impact of a hot, humid and ozone-polluted (O(3)) environment on (1) performance of an 8 km time trial run, (2) pulmonary function, and (3) subjective respiratory symptoms in endurance-trained runners. Using crossover randomized design, 10 male participants (mean V(O)₂(max)= 64.4 mlO(2) kg(-1) min(-1), SD = 4.4) took part in a time trial run under four different conditions: 20 degrees C + 50% relative humidity (rh) (Control), 20 degrees C + 50% rh + 0.10 ppm O(3) (Control + O(3)), 31 degrees C + 70% rh (Heat), 31 degrees C + 70% rh + 0.10 ppm O(3) (Heat + O(3)). Heart rate, ratings of perceived exertion and minute ventilation were collected during the run. Lung function was measured pre and post-exercise. The runners completed a respiratory symptoms questionnaire after each trial. The completion time of both the Heat (32 min 35 s) and Heat + O(3) (33 min 09 s) trials were significantly higher (P < 0.0001) when compared to the Control + O(3) (30 min 27 s) and Control (30 min 15 s) trials. There were no significant changes between pre/post lung function measures or between trials. The effective dose of ozone simulated in the present study did not affect the performance and therefore, ozone-pollution, at an environmentally relevant concentration, did not compound the impairment in performance beyond that induced by a hot, humid environment. PMID:20449752

  14. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  15. Impaired executive functioning after left anterior insular stroke: a case report.

    PubMed

    Markostamou, Ioanna; Rudolf, Jobst; Tsiptsios, Iakovos; Kosmidis, Mary H

    2015-01-01

    Given the insular's anatomic complexity and functional interconnectivity, acute lesions may result in varied clinical presentations, including autonomic, somatosensory, perceptual, motor, affective, and cognitive deficits. Although functional neuroimaging studies have demonstrated its role in executive functions, no clinical manifestations have been reported to date. We present the case of a woman with an acute left anterior insular infarction leading to executive (i.e., word and design fluency, mental flexibility, sustained attention, inhibitory control), but not language, visuoperceptual, or memory impairment. This case confirms the left anterior insula's involvement in executive functioning and suggests that an infarction may result in executive impairment. PMID:25537237

  16. Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

    PubMed Central

    Limjunyawong, Nathachit; Fallica, Jonathan; Ramakrishnan, Amritha; Datta, Kausik; Gabrielson, Matthew; Horton, Maureen; Mitzner, Wayne

    2015-01-01

    The mouse is now the primary animal used to model a variety of lung diseases. To study the mechanisms that underlie such pathologies, phenotypic methods are needed that can quantify the pathologic changes. Furthermore, to provide translational relevance to the mouse models, such measurements should be tests that can easily be done in both humans and mice. Unfortunately, in the present literature few phenotypic measurements of lung function have direct application to humans. One exception is the diffusing capacity for carbon monoxide, which is a measurement that is routinely done in humans. In the present report, we describe a means to quickly and simply measure this diffusing capacity in mice. The procedure involves brief lung inflation with tracer gases in an anesthetized mouse, followed by a 1 min gas analysis time. We have tested the ability of this method to detect several lung pathologies, including emphysema, fibrosis, acute lung injury, and influenza and fungal lung infections, as well as monitoring lung maturation in young pups. Results show significant decreases in all the lung pathologies, as well as an increase in the diffusing capacity with lung maturation. This measurement of lung diffusing capacity thus provides a pulmonary function test that has broad application with its ability to detect phenotypic structural changes with most of the existing pathologic lung models. PMID:25590416

  17. Body Dysmorphic Symptoms, Functional Impairment, and Depression: The Role of Appearance-Based Teasing.

    PubMed

    Weingarden, Hilary; Renshaw, Keith D

    2016-01-01

    Body dysmorphic disorder is associated with elevated social and occupational impairment and comorbid depression, but research on risk factors for body dysmorphic symptoms and associated outcomes is limited. Appearance-based teasing may be a potential risk factor. To examine the specificity of this factor, the authors assessed self-reported appearance-based teasing, body dysmorphic, and obsessive-compulsive symptom severity, functional impairment (i.e., social, occupational, family impairment), and depression in a nonclinical sample of undergraduates. As hypothesized, appearance-based teasing was positively correlated with body dysmorphic symptoms. The correlation between teasing and body dysmorphic symptoms was stronger than that between teasing and obsessive-compulsive symptom severity. Last, body dysmorphic symptom severity and appearance-based teasing interacted in predicting functional impairment and depression. Specifically, appearance-based teasing was positively associated with depression and functional impairment only in those with elevated body dysmorphic symptoms. When a similar moderation was tested with obsessive-compulsive, in place of body dysmorphic, symptom severity, the interaction was nonsignificant. Findings support theory that appearance-based teasing is a specific risk factor for body dysmorphic symptoms and associated functional impairment. PMID:25706778

  18. Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

    PubMed

    Harries, A D; Ade, S; Burney, P; Hoa, N B; Schluger, N W; Castro, J L

    2016-08-01

    In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients. PMID:27393532

  19. Time course of lung function changes in atypical pneumonia.

    PubMed Central

    Benusiglio, L N; Stalder, H; Junod, A F

    1980-01-01

    We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

  20. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    PubMed Central

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

  1. Effects of cooking fuel smoke on respiratory symptoms and lung function in semi-rural women in Cameroon

    PubMed Central

    Mbatchou Ngahane, Bertrand Hugo; Afane Ze, Emmanuel; Chebu, Cyrille; Mapoure, Njankouo Yacouba; Temfack, Elvis; Nganda, Malea; Luma, Namme Henry

    2015-01-01

    Background: Indoor air pollution is a major health problem in the developing world. In sub-Saharan Africa more than 90% of people rely on biomass to meet their domestic energy demands. Pollution from biomass fuel ranks 10th among preventable risk factors contributing to the global burden of diseases. Objectives: The present study aimed to determine the prevalence of respiratory symptoms and the factors associated with reduced lung function in a population of women exposed to cooking fuel smoke. Methods: A cross-sectional study was conducted in a semi-rural area in Cameroon. We compared forced respiratory volume between women using wood (n = 145) and women using alternative sources of energy (n = 155) for cooking. Results: Chronic bronchitis was found in 7·6% of the wood smoke group and 0·6% in the alternative fuels group. We observed two cases of airflow obstruction in the wood smoke group. Factors associated with lung function impairment were chronic bronchitis, use of wood as cooking fuel, age, and height. Conclusion: Respiratory symptoms and reduced lung function are more pronounced among women using wood as cooking fuel. Improved stoves technology should be developed to reduce the effects of wood smoke on respiratory health. PMID:25384259

  2. Rumination prospectively predicts executive functioning impairments in adolescents

    PubMed Central

    Connolly, Samantha L.; Wagner, Clara A.; Shapero, Benjamin G.; Pendergast, Laura L.; Abramson, Lyn Y.; Alloy, Lauren B.

    2014-01-01

    Background and objectives The current study tested the resource allocation hypothesis, examining whether baseline rumination or depressive symptom levels prospectively predicted deficits in executive functioning in an adolescent sample. The alternative to this hypothesis was also evaluated by testing whether lower initial levels of executive functioning predicted increases in rumination or depressive symptoms at follow-up. Methods A community sample of 200 adolescents (ages 12–13) completed measures of depressive symptoms, rumination, and executive functioning at baseline and at a follow-up session approximately 15 months later. Results Adolescents with higher levels of baseline rumination displayed decreases in selective attention and attentional switching at follow-up. Rumination did not predict changes in working memory or sustained and divided attention. Depressive symptoms were not found to predict significant changes in executive functioning scores at follow-up. Baseline executive functioning was not associated with change in rumination or depression over time. Conclusions Findings partially support the resource allocation hypothesis that engaging in ruminative thoughts consumes cognitive resources that would otherwise be allocated towards difficult tests of executive functioning. Support was not found for the alternative hypothesis that lower levels of initial executive functioning would predict increased rumination or depressive symptoms at follow-up. Our study is the first to find support for the resource allocation hypothesis using a longitudinal design and an adolescent sample. Findings highlight the potentially detrimental effects of rumination on executive functioning during early adolescence. PMID:23978629

  3. Impaired Baroreflex Function in Mice Overexpressing Alpha-Synuclein

    PubMed Central

    Fleming, Sheila M.; Jordan, Maria C.; Mulligan, Caitlin K.; Masliah, Eliezer; Holden, John G.; Millard, Ronald W.; Chesselet, Marie-Françoise; Roos, Kenneth P.

    2013-01-01

    Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD). In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn), a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate (HR), computed from R–R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia) to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in HR and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD. PMID:23888153

  4. Functional imaging correlates of impaired distractor suppression following sleep deprivation.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2012-05-15

    Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. PMID:22426349

  5. Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study.

    PubMed

    Lavrenkov, Konstantin; Singh, Shalini; Christian, Judith A; Partridge, Mike; Nioutsikou, Elena; Cook, Gary; Bedford, James L; Brada, Michael

    2009-06-01

    IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung. PMID:18995919

  6. Lung function and six-minute walk test performance in individuals with sickle cell disease

    PubMed Central

    Ohara, Daniela G.; Ruas, Gualberto; Walsh, Isabel A. P.; Castro, Shamyr S.; Jamami, Mauricio

    2014-01-01

    Background Sickle Cell Disease (SCD), which is characterized by a mutation in the gene encoding beta hemoglobin, causes bodily dysfunctions such as impaired pulmonary function and reduced functional capacity. Objective To assess changes in pulmonary function and functional capacity in patients with SCD and to identify the relationships between these variables. Method We evaluated sociodemographic, anthropometric, lung function (spirometry), respiratory (manovacuometer), peripheral muscle strength (Handgrip strength - HS) and functional capacity (i.e., the six-minute walk test) parameters in 21 individuals with SCD (average age of 29±6 years). Shapiro-Wilk, paired Student's, Wilcoxon, Pearson and Spearman correlation tests were used for statistical analyses, and the significance threshold was set at p<0.05. Results A total of 47.6% of the study subjects exhibited an altered ventilation pattern, 42.8% had a restrictive ventilatory pattern (RVP) and 4.8% exhibited a mixed ventilatory pattern (MVP). The observed maximal inspiratory pressure (MIP) values were below the predicted values for women (64 cmH2O), and the maximum expiratory pressure (MEP) values, HS values and distance walked during the 6MWT were below the predicted values for both men (103 cmH2O, 39 Kgf and 447 m, respectively) and women (64 cmH2O; 27 Kgf; 405 m, respectively). Positive correlations were observed between maximum voluntary ventilation (MVV) and MEP (r=0.4; p=0.046); MVV and BMI (r=0.6; p=0.003); and between HS and MIP (r=0.7; p=0.001), MEP (r=0.6; p=0.002), MVV (r=0.5; p=0.015), distance walked in the 6MWT (r=0.4; p=0.038) and BMI (r=0.6; p=0.004). Conclusions SCD promoted changes in lung function and functional capacity, including RVPs and a reduction in the distance walked in the 6MWT when compared to the predictions. In addition, significant correlations between the variables were observed. PMID:24675916

  7. Bisphenol A Exposure is Associated with Decreased Lung Function

    PubMed Central

    Spanier, Adam J.; Fiorino, Elizabeth K.; Trasande, Leonardo

    2014-01-01

    Objective To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. Study design We performed a cross-sectional analysis of a subsample of US children age 6–19 years who participated in the 2007–2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory function in 1 second – FEV1, forced vital capacity – FVC, forced expiratory flow 25–75% – FEF2575, and FEV1/FVC) and with FeNO. Results Exposure and outcome data were available for 661 children. Median BPA was 2.4 ng/ml (IQR: 1.3, 4.1). In multivariable analysis a larger urinary BPA concentration was associated with significantly decreased %FEF2575 (3.7%, 95% CI 1.0, 6.5) and %FEV1/FVC (0.8%, 95% CI 0.1, 1.7) but not %FEV1, %FVC, or FeNO. A child in the top quartile of BPA compared with the bottom quartile had a 10% decrease in %FEF2575 (95% CI −1, −19) and 3% decrease in %FEV1/FVC (95% CI −1, −5). Conclusions BPA exposure was associated with a modest decrease in %FEF2575 (small airway function) and %FEV1/FVC (pulmonary obstruction) but not FEV1, FVC, or FeNO. Explanations of the association cannot rule out the possibility of reverse causality. PMID:24657123

  8. High signal intensity in dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in three patients with impaired renal function and vascular calcification.

    PubMed

    Barbieri, Sebastiano; Schroeder, Christophe; Froehlich, Johannes M; Pasch, Andreas; Thoeny, Harriet C

    2016-05-01

    Gadolinium-based contrast agents (primarily those with linear chelates) are associated with a dose-dependent signal hyperintensity in the dentate nucleus and the globus pallidus on unenhanced T1-weighted MRI following administration to selected patients with normal renal function. The accumulation of gadolinium has also been reported in the skin, heart, liver, lung, and kidney of patients with impaired renal function suffering from nephrogenic systemic fibrosis (NSF). Here we report on three patients with impaired renal function and vascular calcification (two with confirmed NSF) whose unenhanced T1-weighted MRIs showed conspicuous high signal intensity in the dentate nucleus and the globus pallidus after they had been exposed to relatively low doses of linear gadolinium-based contrast agents (0.27, 0.45, and 0.68 mmol/kg). Signal ratios between dentate nucleus and pons and between globus pallidus and thalamus were comparable with previously reported measurements in subjects without renal impairment. Of note, all three analysed patients suffered from transient signs of neurological disorders of undetermined cause. In conclusion, the exposure to 0.27-0.68 mmol/kg of linear gadolinium-based contrast agent was associated with probable gadolinium accumulation in the brain of three patients suffering from impaired renal function and vascular calcification. © 2016 The Authors. Contrast Media & Molecular Imaging published by John Wiley & Sons Ltd. PMID:26929131

  9. Extrarenal citrulline disposal in mice with impaired renal function

    PubMed Central

    Didelija, Inka C.; Fiorotto, Marta L.

    2014-01-01

    The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the “intestinal-renal axis” for arginine synthesis. Although the kidney is the main site for citrulline disposal, it only accounts for ∼60–70% of the citrulline produced. Because the only known fate for citrulline is arginine synthesis and the enzymes that catalyze this reaction are widespread among body tissues, we hypothesized that citrulline can be utilized directly by tissues to meet, at least partially, their arginine needs. To test this hypothesis, we used stable and radioactive tracers in conscious, partially nephrectomized (½ and ⅚) and anesthetized acutely kidney-ligated mouse models. Nephrectomy increased plasma citrulline concentration but did not affect citrulline synthesis rates, thus reducing its clearance. Nephrectomy (⅚) reduced the amount of citrulline accounted for as plasma arginine from 88 to 42%. Acute kidney ligation increased the half-life and mean retention time of citrulline. Whereas the rate of citrulline conversion into plasma arginine was reduced, it was not eliminated. In addition, we observed direct utilization of citrulline for arginine synthesis and further incorporation into tissue protein in kidney-ligated mice. These observations indicate that a fraction of the citrulline produced is utilized directly by multiple tissues to meet their arginine needs and that extrarenal sites contribute to plasma arginine. Furthermore, when the interorgan synthesis of arginine is impaired, these extrarenal sites are able to increase their rate of citrulline utilization. PMID:25056350

  10. The Ways of the Hand: A Study of Hand Function among Blind, Visually Impaired and Visually Impaired Multi-Handicapped Children and Adolescents.

    ERIC Educational Resources Information Center

    Rogow, Sally M.

    1987-01-01

    The manual development of 148 blind, visually impaired, and visually impaired multi-handicapped students, aged 3-19, was studied. Results indicated a significant relationship between object manipulation and speech, and an inverse relationship between object manipulation and stereotypic hand mannerisms. Optimal development of manual functions and…

  11. Differential Item Functioning Comparisons on a Performance-Based Alternate Assessment for Students with Severe Cognitive Impairments, Autism and Orthopedic Impairments

    ERIC Educational Resources Information Center

    Laitusis, Cara Cahalan; Maneckshana, Behroz; Monfils, Lora; Ahlgrim-Delzell, Lynn

    2009-01-01

    The purpose of this study was to examine Differential Item Functioning (DIF) by disability groups on an on-demand performance assessment for students with severe cognitive impairments. Researchers examined the presence of DIF for two comparisons. One comparison involved students with severe cognitive impairments who served as the reference group…

  12. PDGFR signaling blockade in marrow stroma impairs lung cancer bone metastasis.

    PubMed

    Catena, Raúl; Luis-Ravelo, Diego; Antón, Iker; Zandueta, Carolina; Salazar-Colocho, Pablo; Larzábal, Leyre; Calvo, Alfonso; Lecanda, Fernando

    2011-01-01

    Bone microenvironment and cell-cell interactions are crucial for the initiation and development of metastasis. By means of a pharmacologic approach, using the multitargeted tyrosine kinase inhibitor sunitinib, we tested the relevance of the platelet-derived growth factor receptor (PDGFR) axis in the bone marrow (BM) stromal compartment for the initiation and development of lung cancer metastasis to bone. PDGFRβ was found to be the main tyrosine kinase target of sunitinib expressed in BM stromal ST-2 and MC3T3-E1 preosteoblastic cells. In contrast, no expression of sunitinib-targeted receptors was found in A549M1 and low levels in H460M5 lung cancer metastatic cells. Incubation of ST-2 and human BM endothelial cells with sunitinib led to potent cell growth inhibition and induction of apoptosis in a dose-dependent manner. Similarly, sunitinib induced a robust proapoptotic effect in vivo on BM stromal PDGFRβ(+) cells and produced extensive disruption of tissue architecture and vessel leakage in the BM cavity. Pretreatment of ST-2 cells with sunitinib also hindered heterotypic adhesion to lung cancer cell lines. These effects were correlated with changes in cell-cell and cell-matrix molecules in both stromal and tumor cells. Pretreatment of mice with sunitinib before intracardiac inoculation of A549M1 or H460M5 cells caused marked inhibition of tumor cells homing to bone, whereas no effect was found when tumor cells were pretreated before inoculation. Treatment with sunitinib dramatically increased overall survival and prevented tumor colonization but not bone lesions, whereas combination with zoledronic acid resulted in marked reduction of osteolytic lesions and osseous tumor burden. Thus, disruption of the PDGFR axis in the BM stroma alters heterotypic tumor-stromal and tumor-matrix interactions, thereby preventing efficient engagement required for bone homing and osseous colonization. These results support the notion that concomitant targeting of the tumor and

  13. Altered Intranetwork and Internetwork Functional Connectivity in Type 2 Diabetes Mellitus With and Without Cognitive Impairment.

    PubMed

    Yang, Shi-Qi; Xu, Zhi-Peng; Xiong, Ying; Zhan, Ya-Feng; Guo, Lin-Ying; Zhang, Shun; Jiang, Ri-Feng; Yao, Yi-Hao; Qin, Yuan-Yuan; Wang, Jian-Zhi; Liu, Yong; Zhu, Wen-Zhen

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. We investigated whether alterations of intranetwork and internetwork functional connectivity with T2DM progression exist, by using resting-state functional MRI. MRI data were analysed from 19 T2DM patients with normal cognition (DMCN) and 19 T2DM patients with cognitive impairment (DMCI), 19 healthy controls (HC). Functional connectivity among 36 previously well-defined brain regions which consisted of 5 resting-state network (RSN) systems [default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL) and sensorimotor network (SMN)] was investigated at 3 levels (integrity, network and connectivity). Impaired intranetwork and internetwork connectivity were found in T2DM, especially in DMCI, on the basis of the three levels of analysis. The bilateral posterior cerebellum, the right insula, the DMN and the CON were mainly involved in these changes. The functional connectivity strength of specific brain architectures in T2DM was found to be associated with haemoglobin A1c (HbA1c), cognitive score and illness duration. These network alterations in intergroup differences, which were associated with brain functional impairment due to T2DM, indicate that network organizations might be potential biomarkers for predicting the clinical progression, evaluating the cognitive impairment, and further understanding the pathophysiology of T2DM. PMID:27622870

  14. Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin*

    PubMed Central

    Plichta, Jennifer K.; Droho, Steve; Curtis, Brenda J.; Patel, Parita; Gamelli, Richard L.; Radek, Katherine A.

    2014-01-01

    Objectives Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue. Design Experimental mouse scald burn injury. Setting University Research Laboratory. Subjects C57/Bl6 Male mice, 8–12 weeks old. Interventions To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn. Measurements and Main Results Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients. Conclusions These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs

  15. Clinical value of CT-based preoperative software assisted lung lobe volumetry for predicting postoperative pulmonary function after lung surgery

    NASA Astrophysics Data System (ADS)

    Wormanns, Dag; Beyer, Florian; Hoffknecht, Petra; Dicken, Volker; Kuhnigk, Jan-Martin; Lange, Tobias; Thomas, Michael; Heindel, Walter

    2005-04-01

    This study was aimed to evaluate a morphology-based approach for prediction of postoperative forced expiratory volume in one second (FEV1) after lung resection from preoperative CT scans. Fifteen Patients with surgically treated (lobectomy or pneumonectomy) bronchogenic carcinoma were enrolled in the study. A preoperative chest CT and pulmonary function tests before and after surgery were performed. CT scans were analyzed by prototype software: automated segmentation and volumetry of lung lobes was performed with minimal user interaction. Determined volumes of different lung lobes were used to predict postoperative FEV1 as percentage of the preoperative values. Predicted FEV1 values were compared to the observed postoperative values as standard of reference. Patients underwent lobectomy in twelve cases (6 upper lobes; 1 middle lobe; 5 lower lobes; 6 right side; 6 left side) and pneumonectomy in three cases. Automated calculation of predicted postoperative lung function was successful in all cases. Predicted FEV1 ranged from 54% to 95% (mean 75% +/- 11%) of the preoperative values. Two cases with obviously erroneous LFT were excluded from analysis. Mean error of predicted FEV1 was 20 +/- 160 ml, indicating absence of systematic error; mean absolute error was 7.4 +/- 3.3% respective 137 +/- 77 ml/s. The 200 ml reproducibility criterion for FEV1 was met in 11 of 13 cases (85%). In conclusion, software-assisted prediction of postoperative lung function yielded a clinically acceptable agreement with the observed postoperative values. This method might add useful information for evaluation of functional operability of patients with lung cancer.

  16. The aged nonhematopoietic environment impairs natural killer cell maturation and function

    PubMed Central

    Shehata, Hesham M; Hoebe, Kasper; Chougnet, Claire A

    2015-01-01

    Natural killer (NK) cells are critical in eliminating tumors and viral infections, both of which occur at a high incidence in the elderly. Previous studies showed that aged NK cells are less cytotoxic and exhibit impaired maturation compared to young NK cells. We evaluated whether extrinsic or intrinsic factors were responsible for the impaired maturation and function of NK cells in aging and whether impaired maturation correlated with functional hyporesponsiveness. We confirmed that aged mice have a significant decrease in the frequency of mature NK cells in all lymphoid organs. Impaired NK cell maturation in aged mice correlated with a reduced capacity to eliminate allogeneic and B16 tumor targets in vivo. This could be explained by impaired degranulation, particularly by mature NK cells of aged mice. Consistent with impaired aged NK cell maturation, expression of T-bet and Eomes, which regulate NK cell functional maturation, was significantly decreased in aged bone marrow (BM) NK cells. Mixed BM chimeras revealed that the nonhematopoietic environment was a key determinant of NK cell maturation and T-bet and Eomes expression. In mixed BM chimeras, NK cells derived from both young or aged BM cells adopted an ‘aged’ phenotype in an aged host, that is, were hyporesponsive to stimuli in vitro, while adopting a ‘young’ phenotype following transfer in young hosts. Overall, our data suggest that the aged nonhematopoietic environment is responsible for the impaired maturation and function of NK cells. Defining these nonhematopoietic factors could have important implications for improving NK cell function in the elderly. PMID:25677698

  17. Tallying Reference Errors in Narratives: Integrative Language Function, Impairment, and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Thorne, John C.

    2010-01-01

    This study investigates the construct validity of a new measure of Integrative Language functioning, "Tallying Reference Errors In Narratives" (TREIN), by examining the association between previously existing CNS impairment and Expressive Language functioning and elevated outcomes on the TREIN measure "rate of Nominal Reference Errors" (rNRE). The…

  18. Specific Language Impairment and Executive Functioning: Parent and Teacher Ratings of Behavior

    ERIC Educational Resources Information Center

    Wittke, Kacie; Spaulding, Tammie J.; Schechtman, Calli J.

    2013-01-01

    Purpose: The current study used the Behavior Rating Inventory of Executive Function--Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003), a rating scale designed to investigate executive behaviors in everyday activities, to examine the executive functioning of preschool children with specific language impairment (SLI) relative to their…

  19. Family Functioning, Social Impairment, and Symptoms Among Adolescents with Bipolar Disorder

    ERIC Educational Resources Information Center

    Keenan-Miller, Danielle; Peris, Tara; Axelson, David; Kowatch, Robert A.; Miklowitz, David J.

    2012-01-01

    Objective: Impaired social functioning is common among youth with bipolar disorder (BD), emerges in multiple settings, and persists over time. However, little is known about factors associated with poor peer and family functioning in the early-onset form of BD. Using a sample of adolescents with BD I or II, we examined which symptoms of BD,…

  20. Effect of endurance training on lung function: a one year study

    PubMed Central

    Kippelen, P; Caillaud, C; Robert, E; Connes, P; Godard, P; Prefaut, C

    2005-01-01

    Objective: To identify in a follow up study airway changes occurring during the course of a sport season in healthy endurance athletes training in a Mediterranean region. Methods: Respiratory pattern and function were analysed in 13 healthy endurance trained athletes, either during a maximal exercise test, or at rest and during recovery through respiratory manoeuvres (spirometry and closing volume tests). The exercise test was conducted on three different occasions: during basic endurance training and then during the precompetition and competitive periods. Results: During the competitive period, a slight but non-clinically significant decrease was found in forced vital capacity (–3.5%, p = 0.0001) and an increase in slope of phase III (+25%, p = 0.0029), both at rest and after exercise. No concomitant reduction in expiratory flow rates was noticed. During maximal exercise there was a tachypnoeic shift over the course of the year (mean (SEM) breathing frequency and tidal volume were respectively 50 (2) cycles/min and 3.13 (0.09) litres during basic endurance training v 55 (3) cycles/min and 2.98 (0.10) litres during the competitive period; p<0.05). Conclusions: This study does not provide significant evidence of lung function impairment in healthy Mediterranean athletes after one year of endurance training. PMID:16118298

  1. Hemodialysis does not impair ventricular functions over 2 years.

    PubMed

    Duran, Mustafa; Unal, Aydin; Inanc, Mehmet Tugrul; Kocyigit, Ismail; Oguz, Fatih; Ocak, Ayse; Ozdogru, İbrahim; Kasapkara, Ahmet; Karakaya, Ekrem; Oymak, Oktay

    2011-07-01

    We aimed to evaluate the long-term effect of hemodialysis (HD) treatment on left and right ventricular (LV and RV) functions in patients with end-stage renal disease. The study population consisted of 22 patients with newly diagnosed end-stage renal disease. Before an arteriovenous fistula was surgically created for HD, the patients were evaluated by echocardiography for systolic and diastolic functions. After the first HD session (mean 24.22 ± 2.14 months), the second echocardiographic evaluations were performed. Left ventricular and RV functions before and after long-term HD treatment were compared. The mean age was 55 ± 13 years and 10 (45%) of the patients were female. After long-term HD treatment, the isovolumic relaxation time was significantly decreased; however, the peak early (E) and late (A) diastolic mitral inflow velocities, E/A ratio, and deceleration time of E wave were not significantly different from the baseline measurements. Also, there was no significantly change in the early diastolic velocity (Ea) of the lateral mitral anulus and the E/Ea ratio. Pulmonary vein peak diastolic velocity, peak atrial reversal velocity, and peak atrial reversal velocity duration remained almost unchanged even though the pulmonary vein peak systolic velocity and the pulmonary vein peak systolic velocity/pulmonary vein peak diastolic velocity ratio were significantly lower after long-term HD treatment. In addition, LV systolic functions, LV diameters, LV mass index, left atrium size, and RV diastolic functions were not statistically different after long-term HD treatment. The myocardium is exposed to hemodynamic, metabolic, and neuro-humoral abnormalities during HD treatment; however, the long-term effects of HD on ventricular functions are not clearly known. The present study showed that the long-term effects of HD on LV and RV functions were insignificant in patients with end-stage renal disease. We have demonstrated that the LV and RV functions did not change

  2. Impaired T cell function in argininosuccinate synthetase deficiency

    PubMed Central

    Tarasenko, Tatyana N.; Gomez-Rodriguez, Julio; McGuire, Peter J.

    2015-01-01

    ASS1 is a cytosolic enzyme that plays a role in the conversion of citrulline to arginine. In human and mouse tissues, ASS1 protein is found in several components of the immune system, including the thymus and T cells. However, the role of ASS1 in these tissues remains to be defined. Considerable attention has been focused recently on the role of metabolism in T cell differentiation and function. Based on the expression of ASS1 in the immune system, we hypothesized that ASS1 deficiency would result in T cell defects. To evaluate this question, we characterized immune function in hypomorphic fold/fold mice. Analysis of splenic T cells by flow cytometry showed a marked reduction in T cell numbers with normal expression of activation surface markers. Gene therapy correction of liver ASS1 to enhance survival resulted in a partial recovery of splenic T cells for characterization. In vitro and in vivo studies demonstrated the persistence of the ASS1 enzyme defect in T cells and abnormal T cell differentiation and function. Overall, our work suggests that ASS1 plays a role in T cell function, and deficiency produces primary immune dysfunction. In addition, these data suggest that patients with ASS1 deficiency (citrullinemia type I) may have T cell dysfunction. PMID:25492936

  3. Lung function changes in mice sensitized to ammonium hexachloroplatinate.

    PubMed

    Williams, W C; Lehmann, J R; Boykin, E; Selgrade, M K; Lehmann, D M

    2015-01-01

    Occupational exposure to halogenated platinum salts can trigger the development of asthma. The risk to the general population that may result from the use of platinum in catalytic converters and its emerging use as a diesel fuel additive is unclear. To investigate pulmonary responses to platinum, we developed a mouse model of platinum hypersensitivity. Mice were sensitized through application of ammonium hexachloroplatinate (AHCP) to the shaved back on days 0, 5 and 19, and to each ear on days 10, 11 and 12. On days 24 and 29, mice were challenged by oropharyngeal aspiration with AHCP in saline. Before and immediately after challenge, pulmonary responses were assessed using whole body plethysmography (WBP). A dose-dependent increase in immediate responses was observed in AHCP-sensitized and challenged mice. On days 26 and 31, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Lymph node cell counts indicate a proliferative response in lymph nodes draining the sites of application. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 5% eosinophils compared to less than 0.5% in non-sensitized mice (p < 0.05); significant increases in total serum immunoglobulin E were observed for all sensitized mice. Although a second airway challenge on day 29 affected some results, only one airway challenge was needed to observe changes in lung function. PMID:26309092

  4. Obsessive-compulsive disorder is associated with broad impairments in executive function: A meta-analysis

    PubMed Central

    Snyder, Hannah R.; Kaiser, Roselinde H.; Warren, Stacie L.; Heller, Wendy

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a serious and often chronically disabling condition. The current dominant model of OCD focuses on abnormalities in prefrontal-striatal circuits that support executive function (EF). While there is growing evidence for EF impairments associated with OCD, results have been inconsistent, making the nature and magnitude of these impairments controversial. The current meta-analysis uses random-effects models to synthesize 110 previous studies that compared participants with OCD to healthy control participants on at least one neuropsychological measure of EF. The results indicate that individuals with OCD are impaired on tasks measuring most aspects of EF, consistent with broad impairment in EF. EF deficits were not explained by general motor slowness or depression. Effect sizes were largely stable across variation in demographic and clinical characteristics of samples, although medication use, age, and gender moderated some effects. PMID:25755918

  5. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    PubMed Central

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

  6. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders.

    PubMed

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

  7. Acidosis and alkalosis impair brain functions through weakening spike encoding at cortical GABAergic neurons.

    PubMed

    Song, Rongrong; Zhang, Liming; Yang, Zichao; Tian, Xiaoyan

    2011-05-15

    Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of encoding sequential spikes at these GABAergic neurons. The impairments of their spiking are associated with the increases of refractory periods, threshold potential and afterhyperpolarization. Our studies reveal that acidosis and alkalosis impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets may be voltage-gated channels of sodium and potassium. PMID:21353681

  8. Pulmonary functional impairment from years of arc welding

    SciTech Connect

    Kilburn, K.H.; Warshaw, R.H.

    1989-07-01

    The adverse effects of arc welding on pulmonary function have been previously documented. However, in many of these studies, the effects of welding exposure and smoking were not separated. Also, some studies did not adjust for or ignored the effects of asbestosis on pulmonary function. We assessed the long-term effects of welding on pulmonary function in welders who had no evidence of asbestosis on chest radiographs, and adjusted each individual value for height, age, and years of cigarette smoking. The study consisted of 226 male construction welders who had never worked in shipyards. Forced vital capacity (FVC) and flows were measured by spirometry, chest radiographs were obtained and examined for evidence of asbestosis using, and thoracic gas volume (TGV) was determined by planimetry. The subjects were also administered an occupational and respiratory questionnaire. Data on workers with asbestosis (ILO profusion 1/0 or greater) and pleural abnormalities were excluded. The mean age for the 226 subjects without asbestosis was 45 years, mean height was 175.7 cm, and mean duration of welding was 21.3 years. Pulmonary function measurements are presented as mean percentage of predicted (pop) and adjusted for height, age, and years of smoking. In 151 current cigarette smokers, mean midflows and terminal flows were decreased, FEF25-75 to 93.2 pop and FEF75-85 to 91.2 pop, but FVC, forced expiratory volume in one second (FEV1) and TGV were normal. The 43 nonsmokers also had reductions in flows but normal FVC and TGV. Flows in both groups were significantly (p less than 0.05) below those of the referent group. The regression coefficient was -0.0031 for years of welding and FVC pop, -0.0035 for FEV1 pop, and -0.0080 for midflow pop (FEF25-75) (all significant at p less than 0.05), but the coefficient for FEF75-85 pop was not significant.

  9. The Lung Physiome: merging imaging-based measures with predictive computational models of structure and function

    PubMed Central

    Tawhai, Merryn H; Hoffman, Eric A; Lin, Ching-Long

    2009-01-01

    Global measurements of the lung provided by standard pulmonary function tests do not give insight into the regional basis of lung function and lung disease. Advances in imaging methodologies, computer technologies, and subject-specific simulations are creating new opportunities for studying structure-function relationships in the lung through multi-disciplinary research. The digital Human Lung Atlas is an imaging-based resource compiled from male and female subjects spanning several decades of age. The Atlas comprises both structural and functional measures, and includes computational models derived to match individual subjects for personalized prediction of function. The computational models in the Atlas form part of the Lung Physiome project, which is an international effort to develop integrative models of lung function at all levels of biological organization. The computational models provide mechanistic interpretation of imaging measures; the Atlas provides structural data upon which to base model geometry, and functional data against which to test hypotheses. The example of simulating air flow on a subject-specific basis is considered. Methods for deriving multi-scale models of the airway geometry for individual subjects in the Atlas are outlined, and methods for modeling turbulent flows in the airway are reviewed. PMID:20835982

  10. Effect of yoga regimen on lung functions including diffusion capacity in coronary artery disease patients: A randomized controlled study

    PubMed Central

    Yadav, Asha; Singh, Savita; Singh, KP; Pai, Preeti

    2015-01-01

    Background: Lung functions are found to be impaired in coronary artery disease (CAD), congestive heart failure, left ventricular dysfunction, and after cardiac surgery. Diffusion capacity progressively worsens as the severity of CAD increases due to reduction in lung tissue participating in gas exchange. Aims and Objectives: Pranayama breathing exercises and yogic postures may play an impressive role in improving cardio-respiratory efficiency and facilitating gas diffusion at the alveolo-capillary membrane. This study was done to see the effect of yoga regimen on lung functions particularly diffusion capacity in CAD patients. Materials and Methods: A total of 80 stable CAD patients below 65 years of age of both sexes were selected and randomized into two groups of 40 each. Group I CAD patients were given yoga regimen for 3 months which consisted of yogic postures, pranayama breathing exercises, dietary modification, and holistic teaching along with their conventional medicine while Group II CAD patients were put only on conventional medicine. Lung functions including diffusion capacity were recorded thrice in both the groups: 0 day as baseline, 22nd day and on 90th day by using computerized MS medisoft Cardio-respiratory Instrument, HYP’AIR Compact model of cardio-respiratory testing machine was manufactured by P K Morgan, India. The recorded parameters were statistically analyzed by repeated measures ANOVA followed by Tukey's test in both the groups. Cardiovascular parameters were also compared before and after intervention in both the groups. Results: Statistically significant improvements were seen in slow vital capacity, forced vital capacity, peak expiratory flow rate, maximum voluntary ventilation, and diffusion factor/ transfer factor of lung for carbon monoxide after 3 months of yoga regimen in Group I. Forced expiratory volume in 1st sec (FEV1), and FEV1 % also showed a trend toward improvement although not statistically significant. HR, SBP and DBP also

  11. Impaired Right Ventricular-Pulmonary Vascular Function in Myeloproliferative Neoplasms

    PubMed Central

    Roach, Emir C.; Park, Margaret M.; Tang, W.H. Wilson; Thomas, James D.; Asosingh, Kewal; Kalaycio, Matt; Erzurum, Serpil C.; Farha, Samar

    2014-01-01

    Background Increased bone marrow hemangioblast numbers, alterations in erythroid/myeloid lineages, increased reticulin, and greater circulating bone marrow progenitor cells are present in patients with pulmonary arterial hypertension (PAH). The data suggest that myeloid progenitors contribute to the pathogenesis of PAH, but there is little data on prevalence of pulmonary vascular disease among different forms of myeloid diseases. We hypothesized that there would be a higher prevalence of pulmonary vascular disease in myeloproliferative neoplasms that have high circulating progenitor cells, such as myelofibrosis and chronic myelogenous leukemia (CML), as compared to those with low circulating progenitors, as in aplastic anemia. Methods Patients with myelofibrosis, CML and aplastic anemia who underwent echocardiographic evaluation of cardiac function in preparation for bone marrow transplantation at the Cleveland Clinic between 1997–2012 were identified using electronic medical records for demographic data, blood cell counts, and pulmonary function tests. All echocardiograms were uniformly analyzed in a blinded fashion by an advanced sonographer and cardiologist for measures of right and left ventricular function and estimation of pulmonary vascular disease. Results Gender and race distribution between disease groups were similar. Myelofibrosis [N=19] and aplastic anemia [N=30] had increased right ventricle (RV) wall thickness compared to CML [N=82] [RV Thickness (cm): aplastic anemia 0.7 ± 0.1, CML 0.5 ± 0.1 and myelofibrosis 0.7 ± 0.1; p = 0.02]. Patients with myelofibrosis had higher levels of estimated RV systolic pressure as compared to the other groups [RVSP (mmHg): aplastic anemia 29.9 ± 1.5, CML 26.2 ± 1.1 and myelofibrosis 36.7 ± 3.7; p < 0.01]. Conclusion The findings suggest an important role for myeloid progenitors in maintenance of pulmonary-vascular health, in which abnormal myeloproliferative progenitors are associated with right ventricle

  12. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

  13. RELATIONSHIP BETWEEN LUNG FUNCTION AND PHYSICAL CHARACTERISTICS IN YOUNG ADULT BLACK AND WHITE MALES AND FEMALES

    EPA Science Inventory

    The relationships of lung function to physical characteristics in young adults have not been adequately described for different gender-race groups in the United States. s part of a study of the effects of ozone exposure upon Black and White men and women, we measured lung volumes...

  14. Lung transplantation in the rat. III. Functional studies in iso- and allografts

    SciTech Connect

    Marck, K.W.; Prop, J.; Wildevuur, C.R.

    1983-08-01

    Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research.

  15. Impaired mitochondrial function in human placenta with increased maternal adiposity

    PubMed Central

    Mele, James; Muralimanoharan, Sribalasubashini; Maloyan, Alina

    2014-01-01

    The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming. PMID:25028397

  16. Major Depressive Disorder Is Associated with Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review

    ERIC Educational Resources Information Center

    Snyder, Hannah R.

    2013-01-01

    Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have…

  17. White Matter Damage Disorganizes Brain Functional Networks in Amnestic Mild Cognitive Impairment

    PubMed Central

    Garcés, Pilar; López, María Eugenia; Aurtenetxe, Sara; Cuesta, Pablo; Marcos, Alberto; Montejo, Pedro; Yus, Miguel; Hernández-Tamames, Juan Antonio; del Pozo, Francisco; Becker, James T.; Maestú, Fernando

    2014-01-01

    Abstract Although progressive functional brain network disruption has been one of the hallmarks of Alzheimer's Disease, little is known about the origin of this functional impairment that underlies cognitive symptoms. We investigated how the loss of white matter (WM) integrity disrupts the organization of the functional networks at different frequency bands. The analyses were performed in a sample of healthy elders and mild cognitive impairment (MCI) subjects. Spontaneous brain magnetic activity (measured with magnetoencephalography) was characterized with phase synchronization analysis, and graph theory was applied to the functional networks. We identified WM areas (using diffusion weighted magnetic resonance imaging) that showed a statistical dependence between the fractional anisotropy and the graph metrics. These regions are part of an episodic memory network and were also related to cognitive functions. Our data support the hypothesis that disruption of the anatomical networks influences the organization at the functional level resulting in the prodromal dementia syndrome of MCI. PMID:24617580

  18. Effects of pulmonary rehabilitation education for caregivers on pulmonary function and pain in patients with lung cancer following lung resection.

    PubMed

    Jeong, Jong-Hwa; Yoo, Won-Gyu

    2015-02-01

    [Purpose] The purpose of this study was to evaluate the effects of a pulmonary rehabilitation education program for caregivers on patients who underwent lung resection surgery. [Subjects] Subjects who underwent lung resection by visual assisted thoracotomy (VATs) were selected and divided into a control group of 19 and an experimental group of 22. [Methods] The experimental group received a pulmonary rehabilitation education program for caregivers, while the control group received typical care for 4 weeks. This study assessed the subjects 2 weeks (baseline) and 6 weeks after surgery (4 weeks). The forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were measured to evaluate pulmonary function. A visual analogue scale (VAS) was utilized to evaluate pain. [Results] Pulmonary function (FVC and FEV1) increased more in the experimental group compared with the control group. Furthermore, VAS scores were lower in the experimental group compared with the control group. [Conclusion] A pulmonary rehabilitation education program for caregivers had a positive effect on pulmonary function in patients with lung cancer after lung resection. PMID:25729198

  19. Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder

    PubMed Central

    Goikolea, José M.; Bonnin, Caterina M.; Sarró, Salvador; Segura, Barbara; Amann, Benedikt L.; Monté, Gemma C.; Moro, Noemi; Fernandez-Corcuera, Paloma; Maristany, Teresa; Salvador, Raymond; Vieta, Eduard; Pomarol-Clotet, Edith; McKenna, Peter J.

    2016-01-01

    Introduction Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. Methods Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. Results No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. Conclusions Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function. PMID:27448153

  20. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    SciTech Connect

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  1. Conditional deletion of FAK in mice endothelium disrupts lung vascular barrier function due to destabilization of RhoA and Rac1 activities

    PubMed Central

    Schmidt, Tracy Thennes; Tauseef, Mohammad; Yue, Lili; Bonini, Marcelo G.; Gothert, Joachim; Shen, Tang-Long; Guan, Jun-Lin; Predescu, Sanda; Sadikot, Ruxana

    2013-01-01

    Loss of lung-fluid homeostasis is the hallmark of acute lung injury (ALI). Association of catenins and actin cytoskeleton with vascular endothelial (VE)-cadherin is generally considered the main mechanism for stabilizing adherens junctions (AJs), thereby preventing disruption of lung vascular barrier function. The present study identifies endothelial focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that canonically regulates focal adhesion turnover, as a novel AJ-stabilizing mechanism. In wild-type mice, induction of ALI by intraperitoneal administration of lipopolysaccharide or cecal ligation and puncture markedly decreased FAK expression in lungs. Using a mouse model in which FAK was conditionally deleted only in endothelial cells (ECs), we show that loss of EC-FAK mimicked key features of ALI (diffuse lung hemorrhage, increased transvascular albumin influx, edema, and neutrophil accumulation in the lung). EC-FAK deletion disrupted AJs due to impairment of the fine balance between the activities of RhoA and Rac1 GTPases. Deletion of EC-FAK facilitated RhoA's interaction with p115-RhoA guanine exchange factor, leading to activation of RhoA. Activated RhoA antagonized Rac1 activity, destabilizing AJs. Inhibition of Rho kinase, a downstream effector of RhoA, reinstated normal endothelial barrier function in FAK−/− ECs and lung vascular integrity in EC-FAK−/− mice. Our findings demonstrate that EC-FAK plays an essential role in maintaining AJs and thereby lung vascular barrier function by establishing the normal balance between RhoA and Rac1 activities. PMID:23771883

  2. Conditional deletion of FAK in mice endothelium disrupts lung vascular barrier function due to destabilization of RhoA and Rac1 activities.

    PubMed

    Schmidt, Tracy Thennes; Tauseef, Mohammad; Yue, Lili; Bonini, Marcelo G; Gothert, Joachim; Shen, Tang-Long; Guan, Jun-Lin; Predescu, Sanda; Sadikot, Ruxana; Mehta, Dolly

    2013-08-15

    Loss of lung-fluid homeostasis is the hallmark of acute lung injury (ALI). Association of catenins and actin cytoskeleton with vascular endothelial (VE)-cadherin is generally considered the main mechanism for stabilizing adherens junctions (AJs), thereby preventing disruption of lung vascular barrier function. The present study identifies endothelial focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that canonically regulates focal adhesion turnover, as a novel AJ-stabilizing mechanism. In wild-type mice, induction of ALI by intraperitoneal administration of lipopolysaccharide or cecal ligation and puncture markedly decreased FAK expression in lungs. Using a mouse model in which FAK was conditionally deleted only in endothelial cells (ECs), we show that loss of EC-FAK mimicked key features of ALI (diffuse lung hemorrhage, increased transvascular albumin influx, edema, and neutrophil accumulation in the lung). EC-FAK deletion disrupted AJs due to impairment of the fine balance between the activities of RhoA and Rac1 GTPases. Deletion of EC-FAK facilitated RhoA's interaction with p115-RhoA guanine exchange factor, leading to activation of RhoA. Activated RhoA antagonized Rac1 activity, destabilizing AJs. Inhibition of Rho kinase, a downstream effector of RhoA, reinstated normal endothelial barrier function in FAK-/- ECs and lung vascular integrity in EC-FAK-/- mice. Our findings demonstrate that EC-FAK plays an essential role in maintaining AJs and thereby lung vascular barrier function by establishing the normal balance between RhoA and Rac1 activities. PMID:23771883

  3. The profile of executive functioning in amnestic mild cognitive impairment: disproportionate deficits in inhibitory control.

    PubMed

    Johns, Erin K; Phillips, Natalie A; Belleville, Sylvie; Goupil, Diane; Babins, Lennie; Kelner, Nora; Ska, Bernadette; Gilbert, Brigitte; Massoud, Fadi; de Boysson, Chloé; Duncan, Hilary D; Chertkow, Howard

    2012-05-01

    Amnestic mild cognitive impairment (aMCI) represents a group of individuals who are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically conceptualized as involving predominantly deficits in episodic memory, recent studies have demonstrated that deficits in executive functioning may also be present, and thorough categorization of cognitive functioning in MCI may improve early diagnosis and treatment of AD. We first provide an extensive review of neuropsychology studies that examined executive functioning in MCI. We then present data on executive functioning across multiple sub-domains (divided attention, working memory, inhibitory control, verbal fluency, and planning) in 40 aMCI patients (single or multiple domain) and 32 normal elderly controls (NECs). MCI patients performed significantly worse than NECs in all 5 sub-domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub-domains. Impairment on each test was frequent, with 100% of MCI patients exhibiting a deficit in at least one sub-domain of executive functioning. Inhibitory control was the most frequently and severely impaired. These results indicate that executive dysfunction in multiple sub-domains is common in aMCI and highlights the importance of a comprehensive neuropsychological evaluation for fully characterizing the nature and extent of cognitive deficits in MCI. PMID:22370245

  4. Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism. PMID:24192154

  5. Functional limitations in older adults who have cognitive impairment without dementia

    PubMed Central

    Gure, Tanya Ruff; Langa, Kenneth M.; Fisher, Gwenith G.; Piette, John D.; Plassman, Brenda L.

    2013-01-01

    OBJECTIVE Characterize the prevalence of functional limitations among older adults with cognitive impairment without dementia (CIND). METHODS Secondary data analysis was performed using the Aging, Demographics, and Memory Study (ADAMS) dataset. 856 individuals ≥ 71 years old were assigned to 3 diagnostic cognitive categories. A questionnaire was completed by a proxy informant regarding functional limitations for 744 of 856 respondents. RESULTS Of the 744 subjects, 263 (13.9%) had dementia, 201 (21.3%) had CIND, and 280 (64.8%) had normal cognition. Informants reported ≥ 1 IADL limitation in 45% of subjects with CIND compared to 13% of subjects with normal cognition and 85% of subjects with dementia (p < .001). The ADL impairments among individuals with CIND were primarily attributed to physical health problems (n=41; 40%). CONCLUSIONS Many individuals with CIND have impairment in a range of complex and basic daily activities, largely due to physical health problems. PMID:23559664

  6. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy

    PubMed Central

    Kahle, Kristopher T; Merner, Nancy D; Friedel, Perrine; Silayeva, Liliya; Liang, Bo; Khanna, Arjun; Shang, Yuze; Lachance-Touchette, Pamela; Bourassa, Cynthia; Levert, Annie; Dion, Patrick A; Walcott, Brian; Spiegelman, Dan; Dionne-Laporte, Alexandre; Hodgkinson, Alan; Awadalla, Philip; Nikbakht, Hamid; Majewski, Jacek; Cossette, Patrick; Deeb, Tarek Z; Moss, Stephen J; Medina, Igor; Rouleau, Guy A

    2014-01-01

    The KCC2 cotransporter establishes the low neuronal Cl− levels required for GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability. However, no mutations in KCC2 have been documented in human disease. Here, we report two non-synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE). These variants reside in conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly impaired Cl−-extrusion capacities resulting in less hyperpolarized Gly equilibrium potentials (EGly), and impair KCC2 stimulatory phosphorylation at serine 940, a key regulatory site. These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE. PMID:24928908

  7. Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function.

    PubMed

    Pleiss, Melanie M; Sompol, Pradoldej; Kraner, Susan D; Abdul, Hafiz Mohmmad; Furman, Jennifer L; Guttmann, Rodney P; Wilcock, Donna M; Nelson, Peter T; Norris, Christopher M

    2016-09-01

    Mounting evidence suggests that astrocyte activation, found in most forms of neural injury and disease, is linked to the hyperactivation of the protein phosphatase calcineurin. In many tissues and cell types, calcineurin hyperactivity is the direct result of limited proteolysis. However, little is known about the proteolytic status of calcineurin in activated astrocytes. Here, we developed a polyclonal antibody to a high activity calcineurin proteolytic fragment in the 45-48kDa range (ΔCN) for use in immunohistochemical applications. When applied to postmortem human brain sections, the ΔCN antibody intensely labeled cell clusters in close juxtaposition to amyloid deposits and microinfarcts. Many of these cells exhibited clear activated astrocyte morphology. The expression of ΔCN in astrocytes near areas of pathology was further confirmed using confocal microscopy. Multiple NeuN-positive cells, particularly those within microinfarct core regions, also labeled positively for ΔCN. This observation suggests that calcineurin proteolysis can also occur within damaged or dying neurons, as reported in other studies. When a similar ΔCN fragment was selectively expressed in hippocampal astrocytes of intact rats (using adeno-associated virus), we observed a significant reduction in the strength of CA3-CA1 excitatory synapses, indicating that the hyperactivation of astrocytic calcineurin is sufficient for disrupting synaptic function. Together, these results suggest that proteolytic activation of calcineurin in activated astrocytes may be a central mechanism for driving and/or exacerbating neural dysfunction during neurodegenerative disease and injury. PMID:27212416

  8. Evaluation of left and right ventricular myocardial function after lung resection using speckle tracking echocardiography

    PubMed Central

    Wang, Zhenhua; Yuan, Jianjun; Chu, Wen; Kou, Yuhong; Zhang, Xijun

    2016-01-01

    Abstract The impact of major lung resections on myocardial function has not been well-investigated. We aimed to identify this impact through the use of speckle tracking echocardiography (STE) to evaluate the right and left ventricular myocardial function in patients who underwent lung resections. Thirty patients who had lung resections were recruited for this study. Ten patients who underwent pneumonectomies were matched by age and sex, with 20 patients who underwent lobectomies. STE was performed on both right and left ventricle (RV and LV). Strain values of pre and postlung resections were compared in both the pneumonectomy group and the lobectomy group. Comparison between the pneumonectomy group and the lobectomy group was also studied. Left ventricular ejection fraction remained normal (>55%), but significantly decreased after lung resection in both the pneumonectomy group and the lobectomy group. An accelerated heart rate was observed in both groups after lung resection, with the pneumonectomy group demonstrating extra rapid heart rate (P < 0.05). Strain values in the RV and LV decreased in both groups after lung resection, with the pneumonectomy group exhibiting a further decrease in longitudinal strain in LV and RV when compared with the lobectomy group (P < 0.05). Right and left ventricular dysfunction can occur after lung resection regardless of pneumonectomy or lobectomy, and lobectomy may have a less significant impact on myocardial functions. This study demonstrated that STE is able to detect acute cardiac dysfunction after lung resection. PMID:27495031

  9. Hyperpolarized 129Xe MRI: A Viable Functional Lung Imaging Modality?

    PubMed Central

    Patz, Samuel; Hersman, F. William; Muradian, Iga; Hrovat, Mirko I.; Ruset, Iulian C.; Ketel, Stephen; Jacobson, Francine; Topulos, George P.; Hatabu, Hiroto; Butler, James P.

    2008-01-01

    The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used 3He as their imaging agent of choice rather than 129Xe. This preference has been predominantly due to, 3He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized 129Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized 129Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO2) by observation of 129Xe signal decay. We note that the measurement of pO2 by observation of 129Xe signal decay is more complex than that for 3He because of an additional signal loss mechanism due to interphase diffusion of 129Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO2 that accounts for both traditional T1 decay from pO2 and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output. PMID:17890035

  10. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  11. Functional impairment of endothelial cells by the antimycotic amphotericin B.

    PubMed

    Pelzmann, Brigitte; Di Giuro, Cristiana M L; Zorn-Pauly, Klaus; Rossmann, Christine; Hallström, Seth; Groschner, Klaus; Fameli, Nicola

    2016-03-25

    We set out to determine the membrane potential (Vm) of the endothelial cell line EA.hy926 and its sensitivity to the antimycotic amphotericin B (AmB), a commonly used antifungal component in cell culture media. We measured the endothelial Vm under various experimental conditions by patch clamp technique and found that Vm of AmB-treated cells is (-12.1 ± 9.3) mV, while in AmB-untreated (control) cells it is (-57.1 ± 4.1) mV. In AmB-free extracellular solutions, Vm recovered toward control levels and this gain in Vm rapidly dissipated upon re-addition of AmB, demonstrating a rapid and reversible effect of AmB on endothelial Vm. The consequences of AmB dependent alterations in endothelial transmembrane potential were tested at the levels of Ca(2+) signaling, of nucleotide concentrations, and energy metabolism. In AmB-treated cells we found substantially reduced Ca(2+) entry (to about 60% of that in control cells) in response to histamine induced endoplasmic reticulum (ER) Ca(2+) depletion, and diminished the ATP-to-ADP ratio (by >30%). Our data demonstrate a marked and experimentally relevant dependence of basic functional parameters of cultured endothelial cells on the presence of the ionophoric antimycotic AmB. The profound and reversible effects of the widely used culture media component AmB need careful consideration when interpreting experimental data obtained under respective culture conditions. PMID:26902113

  12. Relation between lung function, exercise capacity, and exposure to asbestos cement.

    PubMed Central

    Wollmer, P; Eriksson, L; Jonson, B; Jakobsson, K; Albin, M; Skerfving, S; Welinder, H

    1987-01-01

    A group of 137 male workers with known exposure (mean 20 fibre years per millilitre) to asbestos cement who had symptoms or signs of pulmonary disease was studied together with a reference group of 49 healthy industrial workers with no exposure to asbestos. Lung function measurements were made at rest and during exercise. Evidence of lung fibrosis was found as well as of obstructive airways disease in the exposed group compared with the reference group. Asbestos cement exposure was related to variables reflecting lung fibrosis but not to variables reflecting airflow obstruction. Smoking was related to variables reflecting obstructive lung disease. Exercise capacity was reduced in the exposed workers and was related to smoking and to lung function variables, reflecting obstructive airways disease. There was no significant correlation between exercise capacity and exposure to asbestos cement. PMID:3651353

  13. Pregnancy limits lung function during exercise and depresses metabolic rate in the skink Tiliqua nigrolutea.

    PubMed

    Munns, Suzanne L; Edwards, Ashley; Nicol, Stewart; Frappell, Peter B

    2015-03-01

    High gestational loads have been associated with a range of ecological costs, such as decreased locomotor ability; however, the physiological mechanisms that underpin these changes are poorly understood. In this study, breathing patterns, metabolic rates, lung volume and lung diffusing capacity were measured at rest and during exercise in the pregnant skink Tiliqua nigrolutea. Breathing patterns were largely unaffected by gestation; however, decreases in metabolic rate (rate of oxygen consumption) in the late stages of pregnancy induced a relative hyperventilation. The reductions in metabolic rate during late pregnancy prevent the calculation of the maintenance cost of pregnancy based on post-partum and neonatal metabolic rates. Despite the high relative litter mass of 38.9±5.3%, lung diffusing capacity was maintained during all stages of pregnancy, suggesting that alterations in diffusion at the alveolar capillary membrane were not responsible for the relative hyperventilation. Lung volume was increased during pregnancy compared with non-pregnant females, but lung volume was significantly lower during pregnancy compared with post-partum lung volume. Pregnant females were unable to produce the same metabolic and ventilatory changes induced by exercise in non-pregnant females. This lack of ability to respond to increased respiratory drive during exercise may underpin the locomotor impairment measured during gestation in previous studies. PMID:25788728

  14. Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis.

    PubMed

    Aghaei, Iraj; Nazeri, Masoud; Shabani, Mohammad; Mossavinasab, Marziehsadat; Mirhosseini, Fatemeh Khaleghi; Nayebpour, Mohsen; Dalili, Afshin

    2015-02-01

    Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p < 0.05 was considered statistically significant. BDL rats had an increased level of hepatic enzymes and bilirubin. Impairment of balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study. PMID:25115607

  15. FUNCTIONAL IMPAIRMENT IN ADULTS WITH PAST POSTTRAUMATIC STRESS DISORDER: FINDINGS FROM PRIMARY CARE

    PubMed Central

    Westphal, Maren; Olfson, Mark; Gameroff, Marc J.; Wickramaratne, Priya; Pilowsky, Daniel J.; Neugebauer, Richard; Lantigua, Rafael; Shea, Steven; Neria, Yuval

    2013-01-01

    Background Although many patients with posttraumatic stress disorder (PTSD) experience a reduction in posttraumatic symptoms over time, little is currently known about the extent of their residual functional impairment. This study examines functional impairment in primary care patients with a history of PTSD as compared to patients with current PTSD, and those who never developed PTSD following exposure to trauma. Methods The sample consisted of 321 trauma-exposed low-income, predominantly Hispanic adults attending a large urban primary care practice. PTSD was assessed with the Lifetime Composite International Diagnostic Interview and other psychiatric disorders with the SCID-I. Physical and mental health-related quality of life was assessed with the Medical Outcome Health Survey (SF-12), and functional impairment with items from the Sheehan Disability Scale and Social Adjustment Scale Self-Report. Results Logistic regression analyses controlling for gender, psychiatric comorbidity, and interpersonal traumas showed that although patients with past PTSD function significantly better than patients with current PTSD, they experience persisting deficits in mental health-related quality of life compared to trauma-exposed patients who never developed PTSD. Overall, results revealed a continuum of severity in psychiatric comorbidity, functioning, and quality of life, with current PTSD associated with the most impairment, never having met criteria for PTSD with the least impairment, and history of PTSD falling in between. Conclusions In this primary care sample, adults with a history of past PTSD but no current PTSD continued to report enduring functional deficits, suggesting a need for ongoing clinical attention. PMID:21681868

  16. Degree of Exposure to Domestic Violence, Psychopathology, and Functional Impairment in Children and Adolescents

    ERIC Educational Resources Information Center

    Fernandez, Eduard Bayarri; Ezpeleta, Lourdes; Granero, Roser; de la Osa, Nuria; Domenech, Josep Maria

    2011-01-01

    There are discrepancies about whether children who witness and suffer domestic violence (DV) have similar outcomes in terms of psychopathology. This work examines the relationship between different types of exposure to DV and child psychopathology and functional impairment. One hundred and forty-four Spanish children aged from 4 to 17 years and…

  17. Defeatist Beliefs as a Mediator of Cognitive Impairment, Negative Symptoms, and Functioning in Schizophrenia

    PubMed Central

    Grant, Paul M.; Beck, Aaron T.

    2009-01-01

    Poor social and vocational outcomes have long been observed in schizophrenia. Two of the most consistent predictors are negative symptoms and cognitive impairment. We investigate the hypothesis that cognitive content—defeatist beliefs regarding performance—provides a link between cognitive impairment, negative symptoms, and poor functioning in schizophrenia. A total of 77 individuals (55 patients diagnosed with schizophrenia or schizoaffective disorder and 22 healthy controls) participated in a cross-sectional study of psychopathology. Tests of memory, abstraction, attention, and processing speed, as well as current psychopathology, functioning, and endorsement of defeatist beliefs, were employed. Greater neurocognitive impairment was associated with elevated defeatist belief endorsement, higher negative symptom levels, and worse social and vocational functioning. Notably, statistical modeling indicated that defeatist belief endorsements were mediators in the relationship between cognitive impairment and both negative symptoms and functioning. These effects were independent of depression and positive symptom levels. The results add to the emerging biopsychosocial understanding of negative symptoms and introduce defeatist beliefs as a new psychotherapeutic target. PMID:18308717

  18. Self-Regulation of Emotion, Functional Impairment, and Comorbidity among Children with AD/HD

    ERIC Educational Resources Information Center

    Anastopoulos, Arthur D.; Smith, Taylor F.; Garrett, Melanie E.; Morrissey-Kane, Erin; Schatz, Nicole K.; Sommer, Jennifer L.; Kollins, Scott H.; Ashley-Koch, Allison

    2011-01-01

    Objective: This study investigated the role of self-regulation of emotion in relation to functional impairment and comorbidity among children with and without AD/HD. Method: A total of 358 probands and their siblings participated in the study, with 74% of the sample participants affected by AD/HD. Parent-rated levels of emotional lability served…

  19. Does Change in Functional Performance Affect Quality of Life in Persons with Orthopaedic Impairment?

    ERIC Educational Resources Information Center

    Ostir, Glenn V.; Berges, Ivonne-Marie; Smith, Pamela M.; Smith, David; Rice, Janida L.; Ottenbacher, Kenneth J.

    2006-01-01

    Background and Purpose: Examine the association between change in functional status and quality of life for individuals with orthopaedic impairments approximately 90 days after discharge from in-patient medical rehabilitation. Methods: A retrospective study from 2001 to 2002 using information from the IT HealthTrack database. The study included…

  20. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  1. Assessing ADHD Symptomatic Behaviors and Functional Impairment in School Settings: Impact of Student and Teacher Characteristics

    ERIC Educational Resources Information Center

    DuPaul, George J.; Reid, Robert; Anastopoulos, Arthur D.; Power, Thomas J.

    2014-01-01

    The purpose of the present study was to examine (a) the teacher-reported prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms and associated impairment in a nationally representative sample of children and adolescents and (b) the degree to which prevalence varied as a function of student and teacher characteristics.…

  2. Distinguishing Sluggish Cognitive Tempo from ADHD in Children and Adolescents: Executive Functioning, Impairment, and Comorbidity

    ERIC Educational Resources Information Center

    Barkley, Russell A.

    2013-01-01

    Controversy continues as to whether sluggish cognitive tempo (SCT) is a subtype of attention-deficit/hyperactivity disorder (ADHD) or a distinct disorder. This study examined differences between these disorders in demographics, executive functioning (EF), impairment, and prior professional diagnoses to address the issue. There were 1,800 children…

  3. Working Memory Functioning in Children with Learning Disorders and Specific Language Impairment

    ERIC Educational Resources Information Center

    Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia

    2013-01-01

    Purpose: On the basis of Baddeley's working memory model (1986), we examined working memory functioning in children with learning disorders with and without specific language impairment (SLI). We pursued the question whether children with learning disorders exhibit similar working memory deficits as children with additional SLI. Method: In…

  4. Aberrant Topologies and Reconfiguration Pattern of Functional Brain Network in Children with Second Language Reading Impairment

    ERIC Educational Resources Information Center

    Liu, Lanfang; Li, Hehui; Zhang, Manli; Wang, Zhengke; Wei, Na; Liu, Li; Meng, Xiangzhi; Ding, Guosheng

    2016-01-01

    Prior work has extensively studied neural deficits in children with reading impairment (RI) in their native language but has rarely examined those of RI children in their second language (L2). A recent study revealed that the function of the local brain regions was disrupted in children with RI in L2, but it is not clear whether the disruption…

  5. Cerebral Visual Impairment in Children: A Longitudinal Case Study of Functional Outcomes beyond the Visual Acuities

    ERIC Educational Resources Information Center

    Lam, Fook Chang; Lovett, Fiona; Dutton, Gordon N.

    2010-01-01

    Damage to the areas of the brain that are responsible for higher visual processing can lead to severe cerebral visual impairment (CVI). The prognosis for higher cognitive visual functions in children with CVI is not well described. We therefore present our six-year follow-up of a boy with CVI and highlight intervention approaches that have proved…

  6. Reading Problems, Psychiatric Disorders, and Functional Impairment from Mid- To Late Adolescence.

    ERIC Educational Resources Information Center

    Goldston, David B.; Walsh, Adam; Mayfield Arnold, Elizabeth; Reboussin, Beth; Sergent Daniel, Stephanie; Erkanli, Alaattin; Nutter, Dennis; Hickman, Enith; Palmes, Guy; Snider, Erica; Wood, Frank B.

    2007-01-01

    Objective: To examine psychiatric morbidity and functional impairment of adolescents with and without poor reading skills during mid- to late adolescence. Method: The sample consisted of 188 adolescents, 94 with poor reading skills and 94 with typical reading skills, screened from a larger sample in the public schools at age 15. To assess…

  7. Developmental Language Impairment through the Lens of the ICF: An Integrated Account of Children's Functioning

    ERIC Educational Resources Information Center

    Dempsey, Lynn; Skarakis-Doyle, Elizabeth

    2010-01-01

    The conceptual framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) has the potential to advance understanding of developmental language impairment (LI) and enhance clinical practice. The framework provides a systematic way of unifying numerous lines of research, which have linked a…

  8. 15 CFR 265.38 - Intoxication or other impairment of function.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Intoxication or other impairment of function. 265.38 Section 265.38 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE REGULATIONS GOVERNING TRAFFIC AND CONDUCT REGULATIONS GOVERNING...

  9. A Conceptual Model of the Functioning of Married Persons with Impaired Partners: Spouses of Alcoholic Patients.

    ERIC Educational Resources Information Center

    Finney, John W.; And Others

    1983-01-01

    Presents a conceptual framework of potentially broad applicability in the study of spouses of persons suffering from impairments. The model integrates previous research in the alcoholism field and provides a more comprehensive account of spouse functioning than is afforded by focusing only on partner drinking behavior. (Author/RC)

  10. Young People with Specific Language Impairment: A Review of Social and Emotional Functioning in Adolescence

    ERIC Educational Resources Information Center

    Durkin, Kevin; Conti-Ramsden, Gina

    2010-01-01

    This article provides a review of research into the social and emotional functioning of adolescents with specific language impairment (SLI). In particular, we focus on peer relations, peer friendships, bullying, emotional difficulties and psychiatric difficulties. As a group, adolescents with SLI tend to be more vulnerable to problems in these…

  11. Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Weaver, Kurt E.; Liang, Olivia; Dawson, Geraldine; Aylward, Elizabeth

    2009-01-01

    Amygdala dysfunction has been proposed as a critical contributor to social impairment in autism spectrum disorders (ASD). The current study investigated biochemical abnormalities in the amygdala in 20 high functioning adults with autistic disorder or Asperger's disorder and 19 typically developing adults matched on age and IQ. Magnetic resonance…

  12. Reconceptualizing Treatment Goals from Language Impairment to Functional Limitations: A Case Study

    ERIC Educational Resources Information Center

    Skarakis-Doyle, Elizabeth

    2005-01-01

    This case study of a preadolescent boy with severe expressive and receptive language impairments illustrates treatment focused on the functional limitations on the child's daily academic activities and social participation. Treatment goals incorporated language comprehension objectives into the student's reading program and language use objectives…

  13. A Functional Magnetic Resonance Imaging Investigation of Verbal Working Memory in Adolescents with Specific Language Impairment

    ERIC Educational Resources Information Center

    Weismer, Susan Ellis; Plante, Elena; Jones, Maura; Tomblin, Bruce J.

    2005-01-01

    This study used neuroimaging and behavioral techniques to examine the claim that processing capacity limitations underlie specific language impairment (SLI). Functional magnetic resonance imaging (fMRI) was used to investigate verbal working memory in adolescents with SLI and normal language (NL) controls. The experimental task involved a modified…

  14. Visuo-Spatial Processing and Executive Functions in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Marton, Klara

    2008-01-01

    Background: Individual differences in complex working memory tasks reflect simultaneous processing, executive functions, and attention control. Children with specific language impairment (SLI) show a deficit in verbal working memory tasks that involve simultaneous processing of information. Aims: The purpose of the study was to examine executive…

  15. Asthma phenotypes modify the impact of environmetnal factors on lung function

    EPA Science Inventory

    Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

  16. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

    PubMed Central

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-01-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  17. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    PubMed

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  18. Relationship of small airway chymase-positive mast cells and lung function in severe asthma.

    PubMed

    Balzar, Silvana; Chu, Hong Wei; Strand, Matthew; Wenzel, Sally

    2005-03-01

    Distal lung inflammation may be important in asthma pathophysiology. The goal of this study was to measure cellular inflammation in the large airway and four distal lung regions (small airway inner and outer wall, alveolar attachments, and peripheral alveolar tissue) and to correlate the specific inflammatory cells with several lung function parameters. Sections of concurrently obtained endobronchial and transbronchial/surgical biopsy tissue from 20 individuals with severe asthma were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil, and two mast cell markers (tryptase and chymase). Specific cell distributions were determined and correlated with lung function measures. The number of inflammatory cells generally increased toward the periphery, but the percentage of T-lymphocytes, eosinophils, monocytes/macrophages, and neutrophils remained similar or decreased from large to small airways. In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. Such a relationship was seen only in the small airway/alveolar attachments lung region (r(s) = 0.61-0.89; p lung function in severe asthma. PMID:15563633

  19. The role of executive functions in social impairment in Autism Spectrum Disorder.

    PubMed

    Leung, Rachel C; Vogan, Vanessa M; Powell, Tamara L; Anagnostou, Evdokia; Taylor, Margot J

    2016-01-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by socio-communicative impairments. Executive dysfunction may explain some key characteristics of ASD, both social and nonsocial hallmarks. Limited research exists exploring the relations between executive function and social impairment in ASD and few studies have used a comparison control group. Thus, the objective of the present study was to investigate the relations between executive functioning using the Behavioral Rating Inventory of Executive Functioning (BRIEF), social impairment as measured by the Social Responsiveness Scale (SRS), and overall autistic symptomology as measured by the Autism Diagnostic Observation Schedule (ADOS) in children and adolescents with and without ASD. Seventy children and adolescents diagnosed with ASD and 71 typically developing controls were included in this study. Findings showed that behavioral regulation executive processes (i.e., inhibition, shifting, and emotional control) predicted social function in all children. However, metacognitive executive processes (i.e., initiation, working memory, planning, organization, and monitoring) predicted social function only in children with ASD and not in typically developing children. Our findings suggest a distinct metacognitive executive function-social symptom link in ASD that is not present in the typical population. Understanding components of executive functioning that contribute to the autistic symptomology, particularly in the socio-communicative domain, is crucial for developing effective interventions that target key executive processes as well as underlying behavioral symptoms. PMID:25731979

  20. Honokiol inhibits lung tumorigenesis through inhibition of mitochondrial function.

    PubMed

    Pan, Jing; Zhang, Qi; Liu, Qian; Komas, Steven M; Kalyanaraman, Balaraman; Lubet, Ronald A; Wang, Yian; You, Ming

    2014-11-01

    Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a nonadipogenic PPARγ agonist and capable of inhibiting the growth of a variety of tumor types both in vitro and in xenograft models. However, to fully appreciate the potential chemopreventive activity of honokiol, a less artificial model system is required. To that end, this study examined the chemopreventive efficacy of honokiol in an initiation model of lung squamous cell carcinoma (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU), which is applied topically, reliably triggering the development of SCC within 24 to 26 weeks. Administration of honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol-treated group (P = 0.01) while protecting normal bronchial histology (present in 20.5% of bronchial in control group and 38.5% of bronchial in honokiol-treated group. P = 0.004). P63 staining at the SCC site confirmed the lung SCCs phenotype. In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1-S cell-cycle checkpoint, while also leading to increased apoptosis. Our study showed that interfering with mitochondrial respiration is a novel mechanism by which honokiol changed redox status in the mitochondria, triggered apoptosis, and finally leads to the inhibition of lung SCC. This novel mechanism of targeting mitochondrial suggests honokiol as a potential lung SCC chemopreventive agent. PMID:25245764

  1. FDG-PET Quantification of Lung Inflammation with Image-Derived Blood Input Function in Mice

    PubMed Central

    Locke, Landon W.; Williams, Mark B.; Fairchild, Karen D.; Zhong, Min; Kundu, Bijoy K.; Berr, Stuart S.

    2011-01-01

    Dynamic FDG-PET imaging was used to study inflammation in lungs of mice following administration of a virulent strain of Klebsiella (K.) pneumoniae. Net whole-lung FDG influx constant (Ki) was determined in a compartment model using an image-derived blood input function. Methods. K. pneumoniae (~3 x 105 CFU) was intratracheally administered to six mice with 6 other mice serving as controls. Dynamic FDG-PET and X-Ray CT scans were acquired 24 hr after K. pneumoniae administration. The experimental lung time activity curves were fitted to a 3-compartment FDG model to obtain Ki. Following imaging, lungs were excised and immunohistochemistry analysis was done to assess the relative presence of neutrophils and macrophages. Results. Mean Ki for control and K. pneumoniae infected mice were (5.1 ± 1.2) ×10−3 versus (11.4 ± 2.0) ×10−3 min−1, respectively, revealing a 2.24 fold significant increase (P = 0.0003) in the rate of FDG uptake in the infected lung. Immunohistochemistry revealed that cellular lung infiltrate was almost exclusively neutrophils. Parametric Ki maps by Patlak analysis revealed heterogeneous inflammatory foci within infected lungs. Conclusion. The kinetics of FDG uptake in the lungs of mice can be noninvasively quantified by PET with a 3-compartment model approach based on an image-derived input function. PMID:22187641

  2. Physiologic assessment before video thoracoscopic resection for lung cancer in patients with abnormal pulmonary function

    PubMed Central

    Benattia, Amira; Debeaumont, David; Guyader, Vincent; Tardif, Catherine; Peillon, Christophe; Cuvelier, Antoine

    2016-01-01

    Background Impaired respiratory function may prevent curative surgery for patients with non-small cell lung cancer (NSCLC). Video-assisted thoracoscopic surgery (VATS) reduces postoperative morbility-mortality and could change preoperative assessment practices and therapeutic decisions. We evaluated the relation between preoperative pulmonary function tests and the occurrence of postoperative complications after VATS pulmonary resection in patients with abnormal pulmonary function. Methods We included 106 consecutive patients with ≤80% predicted value of presurgical expiratory volume in one second (FEV1) and/or diffusing capacity of carbon monoxide (DLCO) and who underwent VATS pulmonary resection for NSCLC from a prospective surgical database. Results Patients (64±9.5 years) had lobectomy (n=91), segmentectomy (n=7), bilobectomy (n=4), or pneumonectomy (n=4). FEV1 and DLCO preoperative averages were 68%±21% and 60%±18%. Operative mortality was 1.89%. Only FEV1 was predictive of postoperative complications [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.926–0.991, P=0.016], but there was no determinable threshold. Twenty-five patients underwent incremental exercise testing. Desaturations during exercise (OR, 0.462; 95% CI, 0.191–0.878, P=0.039) and heart rate (HR) response (OR, 0.953; 95% CI, 0.895–0.993, P=0.05) were associated with postoperative complications. Conclusions FEV1 but not DLCO was a significant predictor of pulmonary complications after VATS pulmonary resection despite a low rate of severe morbidity. Incremental exercise testing seems more discriminating. Further investigation is required in a larger patient population to change current pre-operative threshold in a new era of minimally invasive surgery. PMID:27293834

  3. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes

    PubMed Central

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  4. Gross and fine motor function and accompanying impairments in cerebral palsy.

    PubMed

    Himmelmann, K; Beckung, E; Hagberg, G; Uvebrant, P

    2006-06-01

    The aim of this study was to describe and analyze gross and fine motor function and accompanying neurological impairments in children with cerebral palsy (CP) born between 1991 and 1998 in western Sweden. A population-based study comprised 411 children with a diagnosis of CP ascertained at 4 to 8 years of age. Gross Motor Function Classification System (GMFCS) levels were documented in 367 children (205 males, 162 females). Bimanual Fine Motor Function (BFMF) classification levels of 345 of the children and information on learning disability, epilepsy, visual and hearing impairments, and hydrocephalus from 353 children were obtained. For spastic CP, a new classification according to the Surveillance of Cerebral Palsy in Europe of uni- and bilateral spastic CP was applied. GMFCS was distributed at Level I in 32%, Level II in 29%, Level III in 8%, Level IV in 15%, and Level V in 16%. The corresponding percentages for BFMF were 30.7%, 31.6%, 12.2%, 11.9%, and 13.6% respectively. Learning disability was present in 40%, epilepsy in 33%, and severe visual impairment in 19% of the children. Motor function differed between CP types. More severe GMFCS levels correlated with larger proportions of accompanying impairments and, in children born at term, to the presence of adverse peri/neonatal events in the form of intracranial haemorrhage/stroke, cerebral infection, and hypoxic-ischaemic encephalopathy. GMFCS Level I correlated positively to increasing gestational age. We conclude that the classification of CP should be based on CP type and motor function, as the two combine to produce an indicator of total impairment load. PMID:16700930

  5. Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non-smoking mothers.

    PubMed

    Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Mroz, Elzbieta; Klimaszewska-Rembiasz, Maria; Flak, Elzbieta; Edwards, Susan; Spengler, John D

    2010-09-01

    Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM(2.5)), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM(2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow-up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)) and forced expiratory volume in 0.5 s (FEV(0.5)). There were 176 children of non-smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM(2.5) exposure (beta coefficient = -91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV(1) level in children was inversely correlated with prenatal exposure to PM(2.5), and the average FEV(1) deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM(2.5) exposure on FEV(0.5) was proportionally weaker (-72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow

  6. Perinatal stress and early life programming of lung structure and function

    PubMed Central

    Wright, Rosalind J.

    2010-01-01

    Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

  7. Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620

  8. Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease.

    PubMed

    Liu, Yong; Yu, Chunshui; Zhang, Xinqing; Liu, Jieqiong; Duan, Yunyun; Alexander-Bloch, Aaron F; Liu, Bing; Jiang, Tianzi; Bullmore, Ed

    2014-06-01

    Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting

  9. Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

    PubMed

    Proietti, Elena; Riedel, Thomas; Fuchs, Oliver; Pramana, Isabelle; Singer, Florian; Schmidt, Anne; Kuehni, Claudia; Latzin, Philipp; Frey, Urs

    2014-06-01

    Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm. PMID:24696112

  10. Arachidonic acid-derived signaling lipids and functions in impaired healing

    PubMed Central

    Dhall, Sandeep; Wijesinghe, Dayanjan Shanaka; Karim, Zubair A.; Castro, Anthony; Vemana, Hari Priya; Khasawneh, Fadi T.; Chalfant, Charles E.; Martins-Green, Manuela

    2016-01-01

    Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT−/− mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT−/− impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2/B2), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT−/− mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing. PMID:26135854

  11. Arachidonic acid-derived signaling lipids and functions in impaired healing.

    PubMed

    Dhall, Sandeep; Wijesinghe, Dayanjan Shanaka; Karim, Zubair A; Castro, Anthony; Vemana, Hari Priya; Khasawneh, Fadi T; Chalfant, Charles E; Martins-Green, Manuela

    2015-09-01

    Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT(-/-) mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT(-/-) impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α ). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2 /B2 ), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT(-/-) mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing. PMID:26135854

  12. NF-κB inhibitors impair lung epithelial tight junctions in the absence of inflammation.

    PubMed

    Ward, Christina; Schlingmann, Barbara L; Stecenko, Arlene A; Guidot, David M; Koval, Michael

    2015-01-01

    NF-κB (p50/p65) is the best characterized transcription factor known to regulate cell responses to inflammation. However, NF-κB is also constitutively expressed. We used inhibitors of the classical NF-κB signaling pathway to determine whether this transcription factor has a role in regulating alveolar epithelial tight junctions. Primary rat type II alveolar epithelial cells were isolated and cultured on Transwell permeable supports coated with collagen for 5 d to generate a model type I cell monolayer. Treatment of alveolar epithelial monolayers overnight with one of 2 different IκB kinase inhibitors (BAY 11-7082 or BMS-345541) resulted in a dose-dependent decrease in TER at concentrations that did not affect cell viability. In response to BMS-345541 treatment there was an increase in total claudin-4 and claudin-5 along with a decrease in claudin-18, as determined by immunoblot. However, there was little effect on the total amount of cell-associated claudin-7, occludin, junctional adhesion molecule A (JAM-A), zonula occludens (ZO)-1 or ZO-2. Moreover, treatment with BMS-345541 resulted in altered tight junction morphology as assessed by immunofluorescence microscopy. Cells treated with BMS-345541 had an increase in claudin-18 containing projections emanating from tight junctions ("spikes") that were less prominent in control cells. There also were several areas of cell-cell contact which lacked ZO-1 and ZO-2 localization as well as rearrangements to the actin cytoskeleton in response to BMS-345541. Consistent with an anti-inflammatory effect, BMS-345541 antagonized the deleterious effects of lipopolysaccharide (LPS) on alveolar epithelial barrier function. However, BMS-345541 also inhibited the ability of GM-CSF to increase alveolar epithelial TER. These data suggest a dual role for NF-κB in regulating alveolar barrier function and that constitutive NF-κB function is required for the integrity of alveolar epithelial tight junctions. PMID:25838984

  13. Neuropsychological substrates and everyday functioning implications of prospective memory impairment in schizophrenia.

    PubMed

    Twamley, Elizabeth W; Woods, Steven Paul; Zurhellen, Cynthia H; Vertinski, Mary; Narvaez, Jenille M; Mausbach, Brent T; Patterson, Thomas L; Jeste, Dilip V

    2008-11-01

    Individuals with schizophrenia demonstrate impairment in prospective memory (ProM), which describes the multifaceted ability to execute a future intention. Despite its clear implications for everyday functioning, the neuropsychological substrates and functional correlates of ProM impairment in schizophrenia remain poorly understood. In this study, the Memory for Intentions Screening Test (MIST), a standardized measure of ProM, was administered to 72 outpatients with schizophrenia or schizoaffective disorder as part of a comprehensive neuropsychological and psychiatric research evaluation. Results showed that ProM was positively correlated with standard clinical tests of attention, working memory, processing speed, learning, and executive functioning, but not delayed recall. In the context of multiple neuropsychological predictors, learning ability was the only domain that independently contributed to ProM. Importantly, better ProM was predictive of higher functional capacity (as measured by the UCSD Performance-Based Skills Assessment-Brief Version), above and beyond the variability explained by demographic and disease factors. Analysis of component processes revealed that event-based ProM, as well as no response (i.e., omission) and task substitution errors were the strongest predictors of everyday functioning. Overall, these findings suggest that ProM impairment in schizophrenia is associated with multiple cognitive substrates, particularly episodic learning deficits, and plays an important role in everyday living skills. Studies regarding the potential effectiveness of ProM-based remediation strategies to improve functional outcomes in schizophrenia are indicated. PMID:18055178

  14. Sleep impairment, mood symptoms, and psychosocial functioning in adolescent bipolar disorder

    PubMed Central

    Lunsford-Avery, Jessica R.; Judd, Charles M.; Axelson, David A.; Miklowitz, David J.

    2012-01-01

    Few empirical studies have investigated the role of sleep impairment in the course of adolescent bipolar spectrum disorders (BSD). The present study examined the longitudinal associations between sleep disruption, mood symptom severity, and psychosocial functioning in a 2-year follow-up of patients with adolescent BSD. Fifty-three adolescents with BSD (mean [SD] age: 14.6 [1.6]) participated in a two-site randomized trial of family focused treatment for adolescents (FFT-A) or enhanced care, a briefer psychoeducational treatment; both treatments were administered with pharmacotherapy. Sleep disturbance was assessed with the Adolescent Sleep Habits Questionnaire (ASHQ) filled out by patients every 6 weeks in the first study year and every 3 months in the second year. Main outcomes included clinician-rated measures of mania, depression and psychosocial impairment over 2 years. Sleep impairment was significantly associated with mania and depression severity scores and psychosocial impairment ratings across the 2-year follow-up. Despite its efficaciousness in reducing mood symptoms, FFT-A was not more effective than enhanced care in improving sleep habits. Sleep impairment may play a substantial role in the course of adolescent BSD. Youth with BSDs may benefit from targeted psychosocial interventions that emphasize sleep regularity. PMID:22884306

  15. Respiratory symptoms and lung function in oil mist-exposed workers

    SciTech Connect

    Jarvholm, B.; Bake, B.; Lavenius, B.; Thiringer, G.; Vokmann, R.

    1982-06-01

    The prevalence of respiratory symptoms was registered and ventilatory function was determined in 164 men exposed to oil mist. The average exposure time was 16.2 years. One hundred fifty-nine office workers served as controls. The exposed men reported more respiratory symptoms: 14% of the exposed nonsmokers v. 2% of the nonsmoking controls having cough at least three months a year. There were non significant differences between spirometric measurements and chest roentgenograms of the men exposed to oil mist and those of the office workers. The lung function of 25 nonsmoking exposed men was further examined with other lung function tests. The mean values for closing volume, slope of the alveolar plateau, total lung capacity, residual volume, elastic recoil at various lung volumes, and diffusion capacity did not differ significantly.

  16. Influence of Body Composition on Lung Function and Respiratory Muscle Strength in Children With Obesity

    PubMed Central

    Costa Junior, Dirceu; Peixoto-Souza, Fabiana S.; Araujo, Poliane N.; Barbalho-Moulin, Marcela C.; Alves, Viviane C.; Gomes, Evelim L. F. D.; Costa, Dirceu

    2016-01-01

    Background Obesity affects lung function and respiratory muscle strength. The aim of the present study was to assess lung function and respiratory muscle strength in children with obesity and determine the influence of body composition on these variables. Methods A cross-sectional study was conducted involving 75 children (40 with obesity and 35 within the ideal weight range) aged 6 - 10 years. Body mass index, z score, waist circumference, body composition (tetrapolar bioimpedance), respiratory muscle strength and lung function (spirometry) were evaluated. Results Children with obesity exhibited larger quantities of both lean and fat mass in comparison to those in the ideal weight range. No significant differences were found between groups regarding the respective reference values for respiratory muscle strength. Male children with obesity demonstrated significantly lower lung function values (forced expiratory volume in the first second % (FEV1%) and FEV1/forced vital capacity % (FVC%) : 93.76 ± 9.78 and 92.29 ± 3.8, respectively) in comparison to males in the ideal weight range (99.87 ± 9.72 and 96.31 ± 4.82, respectively). The regression models demonstrated that the spirometric variables were influenced by all body composition variables. Conclusion Children with obesity demonstrated a reduction in lung volume and capacity. Thus, anthropometric and body composition characteristics may be predictive factors for altered lung function. PMID:26767078

  17. The severity of shock is associated with impaired rates of net alveolar fluid clearance in clinical acute lung injury.

    PubMed

    Zeyed, Yosaf F; Bastarache, Julie A; Matthay, Michael A; Ware, Lorraine B

    2012-09-15

    The rate of alveolar fluid clearance (AFC) is associated with mortality in clinical acute lung injury (ALI). Patients with ALI often develop circulatory shock, but how shock affects the rate of AFC is unknown. To determine the effect of circulatory shock on the rate of AFC in patients with ALI, the rate of net AFC was measured in 116 patients with ALI by serial sampling of pulmonary edema fluid. The primary outcome was the rate of AFC in patients with shock compared with those without shock. We also tested the effects of shock severity and bacteremia. Patients with ALI and shock (n = 86) had significantly slower rates of net AFC compared with those without shock (n = 30, P = 0.03), and AFC decreased significantly as the number of vasopressors increased. Patients with positive blood cultures (n = 21) had slower AFC compared with patients with negative blood cultures (n = 96, P = 0.023). In addition, the edema fluid-to-plasma protein ratio, an index of alveolar-capillary barrier permeability, was highest in patients requiring the most vasopressors (P < 0.05). Patients with ALI complicated by circulatory shock and bacteremia had slower rates of AFC compared with patients without shock or bacteremia. An impaired capacity to reabsorb alveolar edema fluid may contribute to high mortality among patients with sepsis-induced ALI. These findings also suggest that vasopressor use may be a marker of alveolar-capillary barrier permeability in ALI and provide justification for new therapies that enhance alveolar epithelial and endothelial barrier integrity in ALI, particularly in patients with shock. PMID:22821995

  18. Impaired language function in generalized epilepsy: inadequate suppression of the default mode network.

    PubMed

    Gauffin, Helena; van Ettinger-Veenstra, Helene; Landtblom, Anne-Marie; Ulrici, Daniel; McAllister, Anita; Karlsson, Thomas; Engström, Maria

    2013-07-01

    We aimed to study the effect of a potential default mode network (DMN) dysfunction on language performance in epilepsy. Language dysfunction in focal epilepsy has previously been connected to brain damage in language-associated cortical areas. In this work, we studied generalized epilepsy (GE) without focal brain damage to see if the language function was impaired. We used functional magnetic resonance imaging (fMRI) to investigate if the DMN was involved. Eleven persons with GE and 28 healthy controls were examined with fMRI during a sentence-reading task. We demonstrated impaired language function, reduced suppression of DMN, and, specifically, an inadequate suppression of activation in the left anterior temporal lobe and the posterior cingulate cortex, as well as an aberrant activation in the right hippocampal formation. Our results highlight the presence of language decline in people with epilepsy of not only focal but also generalized origin. PMID:23648277

  19. Changes in Pulmonary Function After Three-Dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy, or Proton Beam Therapy for Non-Small-Cell Lung Cancer

    SciTech Connect

    Lopez Guerra, Jose L.; Gomez, Daniel R.; Zhuang Yan; Levy, Lawrence B.; Eapen, George; Liu, Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-07-15

    Purpose: To investigate the extent of change in pulmonary function over time after definitive radiotherapy for non-small-cell lung cancer (NSCLC) with modern techniques and to identify predictors of changes in pulmonary function according to patient, tumor, and treatment characteristics. Patients and Methods: We analyzed 250 patients who had received {>=}60 Gy radio(chemo)therapy for primary NSCLC in 1998-2010 and had undergone pulmonary function tests before and within 1 year after treatment. Ninety-three patients were treated with three-dimensional conformal radiotherapy, 97 with intensity-modulated radiotherapy, and 60 with proton beam therapy. Postradiation pulmonary function test values were evaluated among individual patients compared with the same patient's preradiation value at the following time intervals: 0-4 (T1), 5-8 (T2), and 9-12 (T3) months. Results: Lung diffusing capacity for carbon monoxide (DLCO) was reduced in the majority of patients along the three time periods after radiation, whereas the forced expiratory volume in 1 s per unit of vital capacity (FEV1/VC) showed an increase and decrease after radiation in a similar percentage of patients. There were baseline differences (stage, radiotherapy dose, concurrent chemotherapy) among the radiation technology groups. On multivariate analysis, the following features were associated with larger posttreatment declines in DLCO: pretreatment DLCO, gross tumor volume, lung and heart dosimetric data, and total radiation dose. Only pretreatment DLCO was associated with larger posttreatment declines in FEV1/VC. Conclusions: Lung diffusing capacity for carbon monoxide is reduced in the majority of patients after radiotherapy with modern techniques. Multiple factors, including gross tumor volume, preradiation lung function, and dosimetric parameters, are associated with the DLCO decline. Prospective studies are needed to better understand whether new radiation technology, such as proton beam therapy or

  20. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  1. Abnormal lung gallium-67 uptake preceding pulmonary physiologic impairment in an asymptomatic patient with Pneumocystis carinii pneumonia

    SciTech Connect

    Reiss, T.F.; Golden, J. )

    1990-05-01

    Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologic tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.

  2. A specific impairment in cognitive control in individuals with high-functioning autism.

    PubMed

    Barbalat, Guillaume; Leboyer, Marion; Zalla, Tiziana

    2014-11-01

    Although it is largely demonstrated that Autism Spectrum Disorders (ASDs) are characterized by executive dysfunctions, little is known about the fine-grained levels of this impairment. Here, we investigated the hierarchical architecture of control modules in autism using an experimental paradigm based upon a multistage model of executive functions. This model postulates that executive functions are hierarchically organized as a cascade of three different control processes, which are implemented according to information conveyed by sensory signals (sensory control), the immediate perceptual context (contextual control), and the temporal episode in which stimuli occur (episodic control). Sixteen high-functioning adults with autism or Asperger Syndrome (HFA/AS) and sixteen matched comparison participants took part in two distinct visuo-motor association experiments designed to separately vary the demands of sensory and episodic controls (first experiment) and contextual and episodic controls (second experiment). Participants with HFA/AS demonstrated no significant differences in performances with comparison participants when they had to control sensory or contextual information. However, they showed decreased accuracy when having to control information related to episodic signals. Remarkably, performances in episodic control were associated to the autism spectrum quotient in both groups, suggesting that this episodic control impairment might be at the core of ASDs. Those results plead for a specific, rather than generalised, deficit in executive functions in autism. Our study contributes to a better understanding of the impaired cognitive processes that are unique to autism and warrants confirmation using other models of executive functions. PMID:25106070

  3. Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome

    PubMed Central

    Fournier, Sara B.; Reger, Brian L.; Donley, David A.; Bonner, Daniel E.; Warden, Bradford E.; Gharib, Wissam; Failinger, Conard F.; Olfert, Melissa D.; Frisbee, Jefferson C.; Olfert, I. Mark; Chantler, Paul D.

    2013-01-01

    MetS is the manifestation of a cluster of cardiovascular (CV) risk factors and is associated with a three-fold increase risk of CV morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to comprehensively examine LV and arterial responses to exercise in MetS individuals without diabetes and/or overt CVD compared to a healthy control population. CV function was characterized using Doppler echocardiography and gas exchange in MetS (n=27) vs. healthy controls (n=20) at rest and during peak exercise. At rest, MetS individuals displayed normal LV systolic function but reduced LV diastolic function vs. healthy controls. During peak exercise, individuals with MetS had impaired contractility; pump performance, and vasodilator reserve capacity vs. controls. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in MetS vs. controls. These findings possess clinical importance as they provide insight to the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of CV morbidity and mortality. PMID:24036595

  4. Association between Lung Function and Vocal Affections Arising from Tobacco Consumption.

    PubMed

    Santos, Karoline Weber Dos; Echeveste, Simone Soares; Vidor, Deisi Cristina Gollo Marques

    2014-01-01

    Introduction Smoking is a major risk factor for numerous diseases; it is necessary to analyze the impact that the habit can have on vocal health. Objectives To determine the influence of smoking on changes in vocal production and lung vital capacity compared with nonsmokers. Methods This cross-sectional study compared smokers and nonsmokers (24 subjects each). Each participant underwent a vocal and spirometric evaluation to measure vital lung capacity. Results The results showed a worsening in lung vital capacity and other parameters of voice in smokers compared with nonsmokers. Furthermore, the decreased pulmonary vital capacity affected the evaluated voice parameters, and decreased carrying capacity was closely related to smoking. The time and amount of consumption had a direct relationship with the vocal and maximum phonation time. Conclusions This study showed that smoking causes voice disorders due to lung weakness. Thus, voice changes are affected both directly by interference of smoking on vocal structures and indirectly by increased weakness, which impairs lung vocal production. PMID:25992056

  5. Association between Lung Function and Vocal Affections Arising from Tobacco Consumption

    PubMed Central

    Santos, Karoline Weber dos; Echeveste, Simone Soares; Vidor, Deisi Cristina Gollo Marques

    2013-01-01

    Introduction Smoking is a major risk factor for numerous diseases; it is necessary to analyze the impact that the habit can have on vocal health. Objectives To determine the influence of smoking on changes in vocal production and lung vital capacity compared with nonsmokers. Methods This cross-sectional study compared smokers and nonsmokers (24 subjects each). Each participant underwent a vocal and spirometric evaluation to measure vital lung capacity. Results The results showed a worsening in lung vital capacity and other parameters of voice in smokers compared with nonsmokers. Furthermore, the decreased pulmonary vital capacity affected the evaluated voice parameters, and decreased carrying capacity was closely related to smoking. The time and amount of consumption had a direct relationship with the vocal and maximum phonation time. Conclusions This study showed that smoking causes voice disorders due to lung weakness. Thus, voice changes are affected both directly by interference of smoking on vocal structures and indirectly by increased weakness, which impairs lung vocal production. PMID:25992056

  6. Kruppel-like factor 5 is required for perinatal lung morphogenesis and function

    PubMed Central

    Wan, Huajing; Luo, Fengming; Wert, Susan E.; Zhang, Liqian; Xu, Yan; Ikegami, Machiko; Maeda, Yutaka; Bell, Sheila M.; Whitsett, Jeffrey A.

    2015-01-01

    The transition to air breathing after birth requires both anatomic and biochemical maturation of the lung. Lung morphogenesis is mediated by complex paracrine interactions between respiratory epithelial cells and mesenchymal cells that direct transcriptional programs guiding patterning and cytodifferentiation of the lung. In the present study, transgenic mice were generated in which the Kruppel-like factor 5 gene (Klf5) was conditionally deleted in respiratory epithelial cells in the fetal lung. Lack of KLF5 inhibited maturation of the lung during the saccular stage of development. Klf5Δ/Δ mice died of respiratory distress immediately after birth. Abnormalities in lung maturation and morphogenesis were observed in the respiratory epithelium, the bronchiolar smooth muscle, and the pulmonary vasculature. Respiratory epithelial cells of both the conducting and peripheral airways were immature. Surfactant phospholipids were decreased and lamellar bodies, the storage form of surfactant, were rarely found. mRNA microarray analysis demonstrated that KLF5 influenced the expression of genes regulating surfactant lipid and protein homeostasis, vasculogenesis, including Vegfa, and smooth muscle cell differentiation. KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth. PMID:18599506

  7. The contribution of executive functions deficits to impaired episodic memory in individuals with alcoholism.

    PubMed

    Noël, Xavier; Van der Linden, Martial; Brevers, Damien; Campanella, Salvatore; Hanak, Catherine; Kornreich, Charles; Verbanck, Paul

    2012-06-30

    Individuals with alcoholism commonly exhibit impaired performance on episodic memory tasks. However, the contribution of their impaired executive functioning to poor episodic memory remains to be clarified. Thirty-six recently detoxified and sober asymptomatic alcoholic men and 36 matched non-alcoholic participants were tested for processing speed, prepotent response inhibition, mental flexibility, coordination of dual-task and a verbal episodic memory task. Compared with non-alcoholic individuals, the alcoholic patients showed impaired executive functions combined with below normal performance on both free and delayed recall. In contrast, processing speed, cued recall and recognition were preserved. Regression analyses revealed that 47% of alcoholics' episodic memory's free recall performance was predicted by mental flexibility and that 49% of their delayed recall performance was predicted by mental flexibility, manipulation of dual-task and prepotent response inhibition. Regarding participants' executive predictors of episodic memory performance, the slopes of β coefficients were significantly different between the two groups, with alcoholics requiring more their executive system than non-alcoholics. Once detoxified, alcoholic patients showed episodic memory deficits mainly characterized by impaired effortful (executive) processes. Compared with controls, patients used effortful learning strategies, which are nonetheless less efficient. PMID:22377577

  8. Attention-deficit-hyperactivity disorder and associated functional impairments in mentally disordered offenders.

    PubMed

    Young, Susan; Gudjonsson, Gisli; O'Rourke, Linda; Woodhouse, Emma; Ashwood, Karen; Murphy, Declan; Asherson, Philip

    2015-12-15

    This study examines the rate of attention-deficit-hyperactivity disorder (ADHD) and associated functional impairments in mentally disordered offenders (MDOs). One hundred and thirty-one male MDOs with a primary diagnosis of either severe mental illness (SMI) or personality disorder (PD) complet