tbuckley/cabot-search huggingface dataset:
Acute smoke exposure decreases bronchial extracellular proteasome concentration
Authors: Stephan J. Schliessmann, Sanja Cicko, Jan Thomassen, Timur Anlasik, Tobias Müller, Marco Idzko, Gernot Zissel, Stephan U. Sixt
Journal: European Respiratory Journal (2011)

Existence of repair mechanisms resulting in bronchial and alveolar protein degradation induced by smoke exposure are largely unknown.

In the alveolar space the presence of an extracellular, biologically active 20S proteasome is recently reported [1,2]. The proteasome is involved in protein degradation and is able to degrade proteins at a high rate, possibly to minimize oncotic pressure [1].

We tested whether the 20S proteasome in the bronchoalveolar space of healthy subjects is influenced by inhalation of tobacco smoke.

Twelve healthy adult subjects underwent bronchoalveolar lavage (BAL) before and after cigarette smoking. To separate bronchiolar and alveolar proteasome concentration, first and second portion of lavage fluid were evaluated separately. Extracellular proteasome concentration was measured by an established in-house ELISA [2] targeting the 20S proteasome subunit a6 (HC2) in cell-free BAL fluid. For statistical evaluation the Wilcoxon signed rank test was applied.

Acute smoke induces a significant decrease in extracellular 20S proteasome concentration in the bronchiolar space (94±55 to 65±50 ng/mL; p<0.05), but no change in the alveolar space (87±48 to 93±55 ng/mL).

Unchanged proteasome concentration in the alveolar fluid showed no artificial elution of the proteasomes by the pre-smoking lavage.

Tobacco smoke inhalation reduces the concentration of extracellular proteasome in the bronchial space and suggests less bronchiolar protein degradation in the acute phase after smoke exposure.

References: 

*   1. Sixt, S.U. et al. Am J Physiol Lung Cell Mol Physiol 2007; 292:L1280-8.

*   2. Sixt, S.U. et al. Am J Respir Crit Care Med 2009; 179:1098-106.
Pulmonary cysts identified on chest CT: are they part of aging change or of clinical significance?
Authors: Tetsuro Araki, Mizuki Nishino, Wei Gao, Josée Dupuis, Rachel K Putman, George R Washko, Gary M Hunninghake, George T O'Connor, Hiroto Hatabu
Journal: Thorax (2015)

<h3>Objective</h3> To investigate the prevalence and natural course of pulmonary cysts in a population-based cohort and to describe the CT image characteristics in association with participant demographics and pulmonary functions. <h3>Materials and methods</h3> Chest CT scans of 2633 participants (mean age 59.2 years; 50% female) of the Framingham Heart Study (FHS) were visually evaluated for the presence of pulmonary cysts and their image characteristics. These findings were correlated with participant demographics and results of pulmonary function tests as well as the presence of emphysema independently detected on CT. The interval change was investigated by comparison with previous CT scans (median interval 6.1 years). <h3>Results</h3> Pulmonary cysts were seen in 7.6% (95% CI 6.6% to 8.7%; 200/2633). They were not observed in participants younger than 40 years old, and the prevalence increased with age. Multiple cysts (at least five) were seen in 0.9% of all participants. Participants with pulmonary cysts showed significantly lower body mass index (BMI) (p&lt;0.001). Pulmonary cysts were most likely to appear solitary in the peripheral area of the lower lobes and remain unchanged or slightly increase in size over time. Pulmonary cysts showed no significant influence on pulmonary functions (p=0.07–0.6) except for diffusing capacity of the lung for carbon monoxide (DLCO) (p=0.03) and no association with cigarette smoking (p=0.1–0.9) or emphysema (p=0.7). <h3>Conclusions</h3> Pulmonary cysts identified on chest CT may be a part of the aging changes of the lungs, occurring in asymptomatic individuals older than 40 years, and are associated with decreased BMI and DLCO. Multiple pulmonary cysts may need to be evaluated for the possibility of cystic lung diseases.
COMPARATIVE NUTRITIONOF IRON AND COPPER
Authors: Joy J. Winzerling,  and John H. Law
Journal: Annual Review of Nutrition (1997)

▪ Abstract The suggestion from nutritional studies with mammals of a link between iron and copper metabolism has been reinforced by recent investigations with yeast cells. Iron must be in the reduced ferrous (FeII) state for uptake by yeast cells, and reoxidation to ferric (FeIII) by a copper oxidase is part of the transport process. Thus, yeast cells deficient in copper are unable to absorb iron. In an analogous way, animals deficient in copper appear to be unable to move FeII out of cells, probably because it cannot be oxidized to FeIII. Invertebrate animals use copper and iron in ways very similar to vertebrates, with some notable exceptions. In the cases where vertebrates and invertebrates are similar, the latter may be useful models for vertebrate metabolism. In cases where they differ (e.g. predominance of serum ferritin in insects, oxygen transport by a copper protein in many arthropods, central importance of phenoloxidase, a copper enzyme in arthropods), the differences may represent processes that are exaggerated in invertebrates and thus more amenable to study in these organisms. On the other hand, they may represent processes unique to invertebrates, thus providing novel information on species diversity.
Value of FOT in young children with SMA
Authors: Leanne Gauld, Lucy Keeling, Peter Sly, Claire Shackleton
Journal: European Respiratory Journal (2013)

Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. Forced Oscillation Technique (FOT) is commercially available for children as young as 2 years and doesn’t require forced expiration.

Aim: To assess usefulness of FOT in young children with SMA.

Methods: Children with SMA aged <10 years were recruited. FOT was performed 3monthly for 12months (5 measurements). Spirometry, assisted and unassisted peak cough flow (PCF) were performed where possible. Height was predicted from ulna length. Predicted values and z-scores were calculated from height. The paired t test compared observed and predicted values. Regression analysis assessed relationships between FVC and PCF to FOT values.

Clinical information included: SMA type, chest infection history, sleep study results, Cobb angle, Valproate use and mobility level. Relationships to FOT were sought using ANOVA.

Results: 12 children (7 male) were recruited, mean age 6.26 (±2.59) years. Rrs8 (mean z-score +2.04 ±2.22, p 0.05) was found between clinical characteristics and FOT values.

Conclusion: FOT testing is feasible in young children with SMA; with abnormal values of Xrs8 and Rrs8 on grouped data. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF). Further research on the value of FOT in managing individuals is warranted.
Afferent and Efferent Interference of Cell-Mediated Cytotoxic Reactions by Heparin
Authors: Chou-Chik Ting
Journal: JNCI Journal of the National Cancer Institute (1976)

Heparin influenced the induction (afferent interference) and effector (efferent interference) phases of cell-mediated cytotoxic reactions against FBL-3 cells, a syngeneic Friend virus-induced leukemia in inbred C57BL/6 mice. Heparin was cytotoxic at high concentrations (greater than or equal to 100 U/ml) and inhibitory for cell-mediated cytotoxic response at lower concentrations (less than or equal to 50 U/ml).
PANERB study: Panitumumab after cetuximab-based regimen failure.
Authors: J. Metges, J. Raoul, N. Achour, O. Capitain, A. Gourlaouen, J. Ramée, J. Egreteau, J. Douillard, S. Traoré, F. Grudé
Journal: Journal of Clinical Oncology (2010)

e14000 Background: Metastatic colorectal cancer management (MRCC) has been clearly improved by targeted therapies such as anti-HER1 drugs. The evaluation of the use of targeted therapies in the real world is strategic to assess health politics. OMIT Bretagne-Pays de Loire is a network of private and public cancer centers. Cohorts of patients concerning Folfiri Bevacizumab treatment (Metges et al, ASCO GI 2009), cost of targeted therapies (Grudé et al, ASCO GI 2009) and AvastErb study (Metges et al, ESMO 2009) have been previously published in this topic. Panitumumab and cetuximab can be used in MRCC but no series of patients is available to evaluate the use of panitumumab monotherapy (PM) after cetuximab irinotecan based regimen (CIBR) failure. Methods: The aim of this study is to assess the succession of cetuximab and then panitumumab regimens in a homogenous series of kras wild-type unresectable MRCC. Sex, age, localization of the primary, successive chemotherapeutic regimens, toxicities, response rate, progression free survival and overall survival have been studied. Results: 32 patients (22 men, 10 women, median age 62 years [43–82]) have been prospectively recruted. All of them have received cetuximab associated with Irinotecan and after progression, monotherapy of panitumumab. The primary was colon (59%), rectum (38%) and double sites (3%). Patients received three to nine successive different lines for MRCC. Manageable toxicities for PM were observed especially acnea. Objective response was obtained in 34.4% with CIBR and in 21.9% with PM. Stable disease was obtained respectively in 15.6% and 9.4% with cetuximab and panitumumab regimens. 54.5% patients with objective response to CIBR have been shown to have objective response to PM too and 18.2% are stable (clinical benefit 72.7%). In case of cetuximab resistance, only 7.7% of patients have an objective response and 7.7% are stable (clinical benefit: 15.4%). PFS for CIBR is 3.5 months. PFS for PM is 3.6 months. Overall survival and PFS curves will be shown during the meeting. Conclusions: Our study shows clearly that patients with progression after response with cetuximab regimen have a real opportunity of clinical benefit (72.7%) with panitumumab monotherapy with a high response rate (54.5%). No significant financial relationships to disclose.
CPAP setting prediction in OSAS patients
Authors: Nikolaos Chavouzis, Katalin Fekete Passa, Afroditi Boutou, Chrysanthi Nakou, Asimina Paspala, Ioannis Stanopoulos, Georgia Pitsiou, Athanasia Pataka, Vasilios Bagalas, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2011)

Aim: To determine how well anthropometric measures and data derived from a diagnostic polysomnography (PSG) study predict the CPAP setting required for therapy.

Method: Data of 158 women and 592 men who had a diagnostic overnight PSG study, a diagnosis of OSAS (Apnea-Hypopnea Index (AHI) >5 and daytime somnolence) and a CPAP titration study were retrospectively analysed. Regression analysis was used to assess the predictive value of age, height, weight, neck, waist and hip circumferences, systolic and diastolic blood pressure at rest and diagnostic PSG data AHI, desaturation index, minimum (min) saturation, average saturation, average apnea-hypopnea duration for determining the required CPAP therapy pressure setting.

Results: Backward regression analysis identified AHI, neck circunference and min saturation as predective parameters for the CPAP pressure. Age and BMI were entered at Step 1 hierarchical regression, explaining 6,1% of the variance in CPAP setting. After entry of AHI, neck circumference and min saturation at Step 2 the total variance explained by the model as a whole was 19,5%, F (5,697) = 35,08, p <0,0005. The three control variables explained an additional 13,8% of the variance in CPAP therapy pressure, after controlling for age and BMI, F change(3,697) = 40,06, p <0,0005. In the final model only the three control variables were statistically significant, with AHI achieving the highest beta value (beta=0,24 p <0,0005), then neck circumference (beta=0,17 p <0,0005) and finally min saturation (beta=-0,14 p =0,001).

Conclusions: OSAS severity, neck circumference and overnight minimum saturation have a statistically significant contribution of 19,5% on the variance of the CPAP therapy pressure, indipendently of the age and the obesity of the subject.
Abstract MP83: Increases in Vigorous Physical Activity Improve Pulse Wave Velocity in Adolescents
Authors: Nicholas M Edwards, Philip R Khoury, Elaine M Urbina
Journal: Circulation (2014)

Introduction: The beneficial effects of vigorous physical activity (VPA) on arterial stiffness have been established, but the effect of changes in VPA over time on these vascular measures is unclear. Hypothesis: Increases in VPA will be associated with improvement in measures of arterial stiffness. Methods: As part of a longitudinal study of the effects of obesity &amp; diabetes on cardiovascular health, 317 subjects (mean age 17.2 years at baseline, 38% male, 63% non-Caucasian) were enrolled and followed up 5 years later. Anthropometrics, accelerometer-measured physical activity, blood pressure, central and peripheral measures of arterial stiffness (pulse wave velocity (PWV), brachial distensibility (BrachD), and augmentation index (AI)), and blood (lipids &amp; metabolic tests) were collected. General linear modeling was performed to test for the independent relationship of change in VPA with change of arterial stiffness. Results: Overall, VPA increased slightly (0.2 minutes) from baseline to follow up. Increased VPA from baseline to follow up was significantly associated (P = 0.0364) with a decrease in PWV but was not associated with a change in BrachD nor AI. The effect of change in VPA on change in PWV was independent of change in glucose (P = 0.024), but not independent of changes in BMI, blood pressure, lipids, or CRP. Conclusions: Increase in vigorous physical activity during late adolescence is significantly associated with improved pulse wave velocity. This relationship may be mediated through improvements in other cardiovascular risk factors such as body mass index, blood pressure, and lipids.
IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease
Authors: Jea-Hyun Baek, Rui Zeng, Julia Weinmann-Menke, M. Todd Valerius, Yukihiro Wada, Amrendra K. Ajay, Marco Colonna, Vicki R. Kelley
Journal: Journal of Clinical Investigation (2015)

Macrophages (Mø) are integral in ischemia/reperfusion injury-incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34-dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34-deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP-ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD.
Molecular epidemiology of Legionnaires‘ disease in Israel
Authors: J. Moran-Gilad, M. Mentasti, T. Lazarovitch, Z. Huberman, T. Stocki, C. Sadik, T. Shahar, E. Anis, L. Valinsky, T.G. Harrison, I. Grotto
Journal: Clinical Microbiology and Infection (2013)
Pharmacists could work in GP premises under proposed new model of care
Authors: Anna Sayburn
Journal: BMJ (2015)

General practitioners could see community pharmacists working as part of their team and on the same premises, under new proposals that aim to make better use of the clinical skills offered by dispensing professionals.

Ash Soni, president of the Royal Pharmaceutical Society, described pharmacists’ current contracts as a “straitjacket” that did not allow community pharmacists the freedom to design services around the needs of local populations.

Some work traditionally undertaken by GPs—such as disease prevention, identifying people with long term conditions, and …
Neurodevelopmental Outcome After Congenital Heart Surgery: Results From an Institutional Registry
Authors: Joseph M. Forbess, Karen J. Visconti, Camille Hancock-Friesen, Robert C. Howe, David C. Bellinger, Richard A. Jonas
Journal: Circulation (2002)

Increased survival in children with critical congenital heart disease (CHD) has raised interest in the neurodevelopmental sequelae of these lesions. This investigation is part of an institutional effort to examine the neurodevelopment of 5-year-old children following repair or palliation of CHD.We performed a battery of neuropsychological tests on a sample of 243 children between 1998 and 2001.In the sample as a whole, mean full-scale (FSIQ), verbal (VIQ), and performance (PIQ) IQ scores were in the normal range (96.8+/-15.9, 97.8+/-14.6, and 96.3+/-17.1, respectively). Anatomic, demographic, and perioperative factors were assessed for impact on neurodevelopment. In multiple regression analysis, lower socioeconomic status (SES) and the diagnosis of velocardiofacial syndrome (VCFS) predicted a lower FSIQ (P=0.01, and P=0.001, respectively). A single ventricle diagnosis (P=0.06), longer postoperative ICU stay (P=0.08), and cumulative duration of hypothermic circulatory arrest (HCA) (P=0.09) approached significance as predictors of lower FSIQ.Children with CHD, on the whole, appear to be performing within the average range in terms of intellectual abilities. Lower SES and VCFS are associated with lower IQ scores. Trends toward worse outcomes were observed in single ventricle patients, biventricular patients with longer postrepair ICU stays, and patients subjected to longer periods of HCA.
Late-breaking abstract: Association of severe exacerbation with FEV1 decline and loss of airway reversibility in asthma
Authors: Kazuto Matsunaga, Tomohiro Ichikawa, Keiichiro Akamatsu, Tsunahiko Hirano
Journal: European Respiratory Journal (2014)

Background: Severe exacerbations involve excessive functional and pathological changes in the airways, which have been suggested to induce airway remodeling leading to loss of lung function in asthma. Objective: To explore whether the severe exacerbation is associated with the decline in post-bronchodilator forced expiratory volume in 1 second (FEV1) and loss of bronchodilator reversibility (BDR). Methods: We investigated the data of a prospective analysis of the association between severe exacerbations and changes in FEV1 and BDR over time in 140 patients with controlled asthma at baseline. Results: A 3-year follow-up assessment was completed in 128 patients. In total, 28 (21.9%) participants experienced at least one severe exacerbation. The exacerbation rate was significantly correlated with an annual decline in FEV1 (ρ = 0.49, p < 0.0001). Both patients with one exacerbation and those with two or more exacerbations had greater declines in FEV1 than patients with no exacerbations (p < 0.01, and p < 0.001, respectively). The mean changes in BDR from baseline to the end of the study, in patients who did or did not experience a severe exacerbation were -1.2% and +0.1% respectively (p < 0.0001). There was a significant correlation between the annual rates of decline in FEV1 and the changes in BDR (r = -0.40, p < 0.0001. Conclusion: Severe exacerbations of asthma were involved in the progression of airflow limitation associated with a decrease in airway reversibility that occurred over time.
NOTES ON A SYMPOSIUM: THE INTERNIST AS A PSYCHIATRIST
Authors: S WOLF, H G WOLFF
Journal: Annals of Internal Medicine (1951)

Article1 January 1951NOTES ON A SYMPOSIUM: THE INTERNIST AS A PSYCHIATRISTSTEWART WOLF, M.D., HAROLD G. WOLFF, M.D., F.A.C.P.STEWART WOLF, M.D.Search for more papers by this author, HAROLD G. WOLFF, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-34-1-212 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFifty years ago in the education of an internist, emphasis rested most heavily upon the teaching of pathology. Since then there has been leading emphasis on physiology and, later, bacteriology. These three disciplines are no less important than they ever have been in the education of a competent internist, but it is becoming increasingly clear that since psychologic phenomena are a part of the problem of every patient for whom he cares and are of leading importance in 40 to 60 per cent of his patients, the internist also needs understanding and skill in the technics of psychiatry.In order...Bibliography1. RipleyWolfWolff HSSHG: Treatment in a psychosomatic clinic, J. A. M. A. 138: 949, 1948. CrossrefMedlineGoogle Scholar2. Groen JJ: Data to be published. Google Scholar3. Dunn WH: Personal communication. Google Scholar4. Atchley DW: Personal communication. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Panel discussion presented before the American College of Physicians in Boston, Mass., on April 18, 1950. Other participants were Dana W. Atchley, Eric Lindemann, Henry M. Thomas, Jr., William H. Dunn and Johannes J. Groen.From the Departments of Medicine and Psychiatry of Cornell University Medical College and the New York Hospital, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPsychiatry and Medical Practice in a General HospitalAcceptance in the therapeutic situation 1 January 1951Volume 34, Issue 1Page: 212-216KeywordsBacteriologyHospital medicine ePublished: 1 December 2008 Issue Published: 1 January 1951 PDF downloadLoading ...
Anxiety, depression and health care utilisation during chronic disease self-management for COPD - an exploratory analysis
Authors: Christian Osadnik, Allison Mandrusiak, Terry Haines, Jennifer Nitz, Angela Chang, Ian A. Yang, Nancy Low-Choy, Claire Jackson, Bill Vicenzino
Journal: European Respiratory Journal (2014)

Introduction: Difficulty accessing pulmonary rehabilitation (PR) and the high prevalence of anxiety and depression in COPD has seen increased interest in alternative models of care such as the Stanford Chronic Disease Self-Management (CDSM) program. The effects of anxiety and depression on CDSM, and the effects of CDSM on healthcare utilisation (HCU) are largely unknown.  Aim: To determine the effect of anxiety and depression on HCU in participants undergoing CDSM.  Methods: Retrospective analysis of a multicentre randomised trial of PR vs CDSM. 169 participants (mean age 68 years, mean FEV 1  52% pred, 73 female) attended PR (8 weeks, 16 sessions; n=85) or CDSM (6 weeks, 6 sessions; n=84). Hospital anxiety and depression scale (HADS) and self-reported HCU were recorded after 3,6 and 9 months. Data were analysed via generalized estimating equations.  Results: Across both groups, participants with high anxiety scores (≥10) had a trend towards more hospital days than others (p=0.08), whilst anxiety 9responders9 (reduction ≥1.5 points) had more frequent hospitalisations (beta=0.09, SE=0.05; p=0.04). Within the CDSM group, high anxiety was associated with more hospital days (beta=2.77, SE=1.01; p=0.01) but not a significantly greater need for hospitalisation (p=0.06) or more frequent hospitalisations (p=0.20). High levels of depression did not affect any outcomes relating to hospital admissions. The effect of CDSM on hospitalisations did not differ between anxiety or depression 9responders9 and 9non-responders9.  Conclusion: The effectiveness of Stanford CDSM on HCU in people with COPD appears to be influenced by high levels of anxiety but not depression.