tbuckley/cabot-search huggingface dataset:
Mycobacterium bovis (BCG) Infection of the Lymph Nodes of Normal, Immune, and Cortisone-Treated Guinea Pigs 2
Authors: Frank M. Collins, Linda Auclair, George B. Mackaness
Journal: JNCI Journal of the National Cancer Institute (1977)

Strain-2 inbred guinea pigs were infected intradermally with 10(5)-10(7) viable BCG (Pasteur) organisms by means of multiple scarifications of shaven midflank skin. The spread of the BCG to the draining lymph nodes and on to the spleen was followed quantitatively for 28 days. The population of bacilli at the inoculation site increased as much as tenfold the first 14 days. The number of viable BCG organisms recovered from the primary draining superficial dorsal axillary and inguinal lymph nodes varied from 0.1 to 1.0% of the inoculum, with a further tenfold to 100-fold drop in counts for the secondary subclavian and lumbar lymph nodes. The bacterial counts for the various nodes increased substantially the first 14 days. By 28 days, as many as 1,000 viable bacilli were recovered from the spleen. Increasing the inoculum size or the number of inoculation sites increased the primary node counts and promoted a more extensive and rapid spread by the BCG population to the secondary lymph nodes and spleen. Prior vaccination of the host with living BCG decreased the spread of the BCG inoculum from the scarification site to the various draining lymph nodes. Multiple injections of cortisone tended to reverse this effect.
Lobectomy at patients with lung cancer and a chronic obstructive pulmonary disease as analogue of lung volume reduction surgery in COPD patients: To do or not to do?
Authors: Dmitry Bazarov, Kuldash Abdumuradov, Denis Fedorov, Vladimir Parshin
Journal: European Respiratory Journal (2013)

Background. In Russia annually reveal about 60000 new cases of lung cancer (LC). About half of patients with lung cancer have chronic obstructive pulmonary disease (COPD).  Aims. To study results of lobectomy in patients with LC and COPD as procedure directed on elimination of LC and reduction of respiratory failure.  MATERIALS AND METHODS. 27 patients with LC and with heavy COPD were managed. Men were 25. The age varied from 57 to 72 years. The stage of a LC was IB to IIB. All patients had obstruction FEV1 21±5%, heavy dyspnea 3,5-4 points (MRC) and hyperinflation TLC – 138±18%, RV – 294±87%, RV/TLC – 70±8%. Gas analysis found PaO2 – 73±13 mm hg and PaCO2 - 41±7 mm hg. In all patient lobectomy with an expanded limfodissection performed.  RESULTS. There were no lethality. The complications included COPD exacerbation in 15 patients, pneumonia in 11 patients, long air leaks on drainages in 11 patients, formation of a residual cavity in 4 patients that demanded introduction of the endobronchial valve. Since 6th month post surgery (p.s.), in 17 patients dyspnea decreased by 1-2 degrees. In 1 and 2 y p.s. FEV1 increased for 17% and 19%, RV decreased 87% and 89%, RV/TLC - decreased 10% and 16%. In 1 and 2 year p.s. dyspnea lowered by 1,5 and 1,4 points. Recurrence and progressing of LC was in 5 patients in 1 year after operation and in 8 cases in 2 years after operation.  CONCLUSIONS. Thus lobectomy in patients with a cancer of lung I-II st. without defeat of mediastinal lymph nodes and with heavy COPD may be important procedure as helps not only to remove a tumor, but also to reduce dyspnoe and to improve quality of life.
Pulmonary hypertension associated with congenital heart disease (PH-CHD): Results from the ASPIRE registry
Authors: Sheila Ramjug, Judith Hurdman, Nehal Hussain, Ian Sabroe, Charlie Elliot, David Kiely, Robin Condliffe
Journal: European Respiratory Journal (2013)

Introduction: Current guidelines describe 4 groups of PH-CHD: A Eisenmengers; B Large defect with left-right shunt; C Small defect; D Previously closed defect. There are sparse data comparing these groups.

Methods: Data for all 198 PH-CHD pts in the ASPIRE (Assessing the Spectrum of Patients Identified at a REferral centre) registry were reviewed.

Results: Although group B had milder haemodynamics and a lower proportion in functional class (FC) III or IV compared with groups C and D (Table) there was no significant difference in survival (Figure). In group A, Age, FC, DLCO and incremental shuttle walking distance (ISWD) predicted survival at univariate, and ISWD at multivariate analysis, while survival in the 23% with trisomy-21 was not different to those without trisomy-21.

Conclusions: Despite differing characteristics, survival of PH-CHD pts referred to specialist centres does not significantly differ between the 4 groups. Further details of medical and interventional therapies will be presented.

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Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia
Authors: David Rodríguez, Gabriel Bretones, Víctor Quesada, Neus Villamor, Javier R. Arango, Armando López-Guillermo, Andrew J. Ramsay, Tycho Baumann, Pedro M. Quirós, Alba Navarro, Cristina Royo, José I. Martín-Subero, Elías Campo, Carlos López-Otín
Journal: Blood (2015)
Extended thoracoscopy: a biopsy method to be used in case of pleural adhesions
Authors: JP Janssen, C Boutin
Journal: European Respiratory Journal (1992)

Extended thoracoscopy (ET) allows several large biopsies to be taken in patients with thick adhesions of the pleura when normal thoracoscopy is impossible. Twenty patients with undiagnosed pleural effusion or thickening and two with associated pulmonary tumour close to the chest wall underwent ET because closed adhesions prevented the induction of an artificial pneumothorax. Under local anaesthesia and neuroleptanalgesia, at the site of suspected lesions on computed tomographic (CT) scan, a cutaneous incision of 3-4 cm is made on the appropriate intercostal space. After dissection with blunt scissors, the operator introduces his finger to create a space in the pleural cavity. The thoracoscope is inserted to inspect the pleura and to take several biopsies for histopathological examination. A chest tube is inserted for a few minutes after checking airtightness and haemostasis. The procedure is well-tolerated. In three cases no pleural biopsy could be taken; in three patients a false negative diagnosis was observed. A correct diagnosis was obtained in 16 out of 19 patients (84%). If performed by a pulmonologist experienced with thoracoscopy ET is a rapid, safe and efficient method to obtain biopsies in cases where normal thoracoscopy after induction of a pneumothorax is not possible. It considerably reduces the need for open thoracotomy.
TNF ± mediates ectodomain shedding of BMPR-II: A potential role in pulmonary arterial hypertension
Authors: Liam Hurst, Benjamin Dunmore, Paul Upton, Nicholas Morrell
Journal: European Respiratory Journal (2013)

Background: Mutations in BMP type II receptor (BMPR-II) account for 70% of heritable pulmonary arterial hypertension (PAH) cases, but low penetrance (∼20%) in mutation carriers implies a ‘second hit’ is required for disease initiation. Inflammation has been implicated, yet the molecular mechanisms by which it influences pathology are unclear.  Aim: To investigate a possible molecular link between a key mediator of inflammation, tumour necrosis factor alpha (TNFα), and BMPR-II.  Methods: Human pulmonary arterial smooth muscle cells (PASMCs) were stimulated with TNFα (1ng/mL). Immunoprecipitation, western blotting, quantitative PCR, plasmid DNA transfection, site-directed mutagenesis, RNA interference and pharmacological inhibitors were used to assess the impact of TNFα on BMPR-II and BMP signalling pathways.  Results: TNFα stimulation reduced BMPR-II mRNA and protein expression, leading to loss of BMP signalling, as evidenced by abrogated Smad 1/5 and ID1 activation. Notably, a low molecular weight form of BMPR-II accumulated in PASMC lysates following prolonged TNFα exposure: identified as a C-terminal cleavage product of BMPR-II. Furthermore, the N-terminal ectodomain of BMPR-II could be immunoprecipitated from conditioned media. TNFα increased expression of two A Disintegrin and Metalloproteinase Domain-containing proteins (ADAMs); ADAM10 and ADAM17. Pharmacological blockade and RNA interference revealed both proteases were capable of BMPR-II cleavage. Mutation of the putative cleavage site restored BMP signalling.  Conclusions: We identified a novel mechanism by which TNFα impairs BMP signalling. These findings highlight TNFα as a potential therapeutic target in PAH.
Ecological information and prospective control without mental representation
Authors: Nam-Gyoon Kim, Judith A. Effken
Journal: Behavioral and Brain Sciences (2001)

We agree with the authors that an adequate account of the perception-action interface is needed. However, we believe that the answer will not be found in a common representational structure encoding distal events, as the authors propose, but in Gibson's notion of ecological information, which, as we demonstrate, specifies not only perspective but also prospective and retrospective states of affairs.
Comparison of knowledge, attitude and practice of tobacco use among private (Pvt) and public (Publ) high school teachers and their policies
Authors: Maria Malik, Ashok Kumar, Shaista Ghazal, Quratul Ain Malik, Umair Misbah, Nadeem Rizvi
Journal: European Respiratory Journal (2013)

Background:Teachers being very influential can alter their student’s perception on smoking drastically.  Objectives: To compare knowledge,attitude and practice of tobacco use among Pvt. and Publ. high school teachers and their Policies.  Methodology:A cross sectional study, done in Karachi,Pakistan using WHO global professional survey Questionnaire.  Results:Out of 1000 questionnaires distributed,652 teachers responded (53.8% Pvt,46.2% Publ).Cigeratte use was more common in Pvt(25.7%) than Publ(21.2%) with 8% Pvt and 6.6% Publ teachers using it in school.Smokeless tobacco was seen more in Publ teachers with 29.8% using it on premises(0.000). Pvt teachers taught more about hazards of tobacco as primary responsibility than Publ (0.002).On youth tobacco use 50.3% Publ and 10.9% Pvt teachers showed no concern(0.000) with 19.9% Publ and 13.7% Pvt teachers refusing to admit their influence on students tobacco use(0.015).Publ teachers were more unaware of harmfulness of passive smoking(0.000),lacked the knowledge that tobacco is addictive(0.007) and were unaware it causes heart diseases(0.019). School policy of tobacco use on students was negated by 49.7% Publ and 22.3% Pvt teachers,results were similar in school personnels(0.000).Absence of tobacco use prevention in curriculum was admitted by 37.4% Pvt and 55.6% Publ teachers (0.000) while 95.4% Publ and 90.3% Pvt teachers had no training to prevent its use (0.009).  Conclusion:Tobacco use is prevalent in Pvt and Publ school teachers with later being more serious.Effective educational programs,school policies and training are required for teachers so they can educate students and prevent this dilemma.
Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens
Authors: Shikhar Uttam, Hoa V. Pham, Justin LaFace, Brian Leibowitz, Jian Yu, Randall E. Brand, Douglas J. Hartman, Yang Liu
Journal: Cancer Research (2015)

Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Therefore, frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Here, we present a new method to predict cancer progression risk via nanoscale nuclear architecture mapping (nanoNAM) of unstained tissue sections based on the intrinsic density alteration of nuclear structure rather than the amount of stain uptake. We demonstrate that nanoNAM detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis who did and did not develop colon cancer up to 13 years after their initial colonoscopy. NanoNAM of the initial biopsies correctly classified 12 of 15 patients who eventually developed colon cancer and 15 of 18 who did not, with an overall accuracy of 85%. Taken together, our findings demonstrate great potential for nanoNAM in predicting cancer progression risk and suggest that further validation in a multicenter study with larger cohorts may eventually advance this method to become a routine clinical test.
Global burden of non-cystic fibrosis bronchiectasis: A simple epidemiological analysis
Authors: Eva Polverino, William Cacheris, Cara Spencer, Elisabeth Operschall, Anne E. O'Donnell
Journal: European Respiratory Journal (2012)

Introduction   Non-cystic fibrosis bronchiectasis (NCFB) is a relatively rare condition in which potential respiratory pathogens frequently colonize the lungs, often leading to exacerbations. Although classified as an orphan disease in the US, limited data are available to quantify the burden of NCFB worldwide.   Methods   A systematic search was performed in MEDLINE and PubMed for original articles containing epidemiological information on: the rate of NCFB in the general population; the age and sex distribution of the patients; the proportion of those with culture-positive sputum; and the frequency of exacerbations. The search yielded 97 publications: 33 gave meaningful data for this study. Information was aggregated using a weighted average across multiple published studies to derive factors that were applied to all countries in the analysis.   Results   The prevalence rate of NCFB in the general population was calculated to be 39.9 cases per 100,000. In total, 75.8% of patients have culture-positive sputum and 48% experience ≥2 exacerbations per year. Table 1 shows single country data.   Conclusions   This epidemiology calculation demonstrates that there are marked global numbers of NCFB patients suffering from frequent exacerbations who may need therapies that could potentially reduce exacerbations. More data from individual regions and countries are needed to better estimate global epidemiology of NCFB.
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Authors: E L Wynder, J R Hebert, G C Kabat
Journal: JNCI Journal of the National Cancer Institute (1987)

An international comparison study of the relationship among dietary predictors, tobacco consumption, income, and truncated age-adjusted lung cancer mortality was conducted with the use of time-lagged data available for 43 countries. A regression analysis weighting each country by the square root of the appropriate population and adjusting for several covariates showed that calories from dietary fat were highly significantly associated (P less than .0001) with lung cancer mortality. This finding was obtained after accounting for disappearance data for tobacco (P less than .0001), the dominant risk factor for lung cancer, and total nonfat calories (P less than .002). Other covariates included per capita gross national product and proportion of calories from fruits, vegetables, roots, tubers, and pulses. Weaknesses of this study, statistical considerations, biologic plausibility, in particular the modulation of tobacco-smoke carcinogens by lipids in the lung, and suggestions for future study are discussed.
A peripheral HRV-16-driven fingerprint is enriched in severe asthma patients in absence of an active exacerbation
Authors: Patrick Branigan, Ronald Turner, Aleksandar Stojmirovic, Matthew Loza, Alfred Delvecchio, Stanley Marciniak, Nancy Peffer, Philip Silkoff, Radu Dobrin, Frederic Baribaud
Journal: European Respiratory Journal (2014)

Background: Human rhinovirus 16 (HRV-16) is the leading cause of viral-induced exacerbations in asthma. Biomarkers that identify patients at risk of exacerbations are emerging but remain limited.

Methods: To characterize a Good Manufacturing Practice (GMP) pool of HRV-16, normal healthy volunteers (NHV) were challenged with HRV-16 (n=30; [NCT01466738][1]) and assessed for clinical response and biomarkers. RNA was isolated from whole blood and transcriptional profiles were evaluated.

Results: Nine gene co-expression modules representing varying peripheral acute response profiles to HRV-16 infection were identified, including an interferon response module that peaked at days 3-4 and resolved by day 6. Peripheral transcriptional profiles were also analyzed in the context of moderate and severe asthma biologic networks derived from baseline bronchial transcriptional profiles independently obtained in a Janssen non-interventional Airway Disease Endotyping for Personalized Treatment of Asthma and COPD profiling study (ADEPT) (n= 150; [NCT01274507][2]). Specific components of the acute peripheral HRV-16 fingerprint were shown to significantly correlate with NF-kβ and pattern recognition receptor signaling nodes in the moderate asthma network, and type I interferon nodes in the severe asthma network, both derived from the ADEPT study.

Conclusions: These data show that an HRV-16 fingerprint, indicative of an active innate immune axis, is enriched in severe asthma patients in absence of clinical signs of a viral infection or active exacerbation, suggesting a dysregulated baseline innate immune response profile. The link to a heightened risk of exacerbations is currently being explored.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01466738&atom=%2Ferj%2F44%2FSuppl_58%2FP241.atom
 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01274507&atom=%2Ferj%2F44%2FSuppl_58%2FP241.atom
Treatment of hydatid disease in childhood with mebendazole
Authors: A Gocmen, MF Toppare, N Kiper
Journal: European Respiratory Journal (1993)

The general characteristics of 56 childhood cases of cystic hydatid disease were analysed and the results of mebendazole therapy versus surgery were verified. Pulmonary radiograms and ultrasonography were used in the diagnosis. The cysts were localized primarily to the lungs. Twenty seven patients were surgically-treated, with eight having recurrence after a mean period of 3.6 yrs. Thirty patients received regular mebendazole treatment, in a dose of 50 mg.kg-1 with a mean duration of treatment of 11.7 months. Twenty one patients were cured and discontinued the therapy. Nine still use the drug, seven of whom have had dramatic improvement, while the other two have minimal radiographic changes but subjective improvement in general condition. The lung cysts vanished leaving minimal scars, whilst the liver cysts turned into inactive forms. The surgically-treated and drug-treated groups were similar in age, duration and severity of the disease. The recurrence rate of drug-treated children (1 out of 20) was lower than that of the surgically-treated children (8 out of 27); however, this was not statistically significant.
A phase Ib study of telatinib (BAY 57–9352), a VEGFR-2 inhibitor, in combination with docetaxel in patients with advanced solid tumours
Authors: H. M. Shaw, L. R. Molife, J. Spicer, V. Karavasilis, C. Marriott, T. J. Ong, L. Tate, E. Brendel, O. Christensen, J. S. de Bono
Journal: Journal of Clinical Oncology (2007)

14035 Background: Telatinib (BAY 57–9352) inhibits VEGFR-2 and VEGFR-3 tyrosine kinases, and PDGFR-β and c-Kit. Preclinical data suggests that targeting VEGFR signaling increases antitumor activity. Methods: This trial investigated the safety, pharmacokinetics (PK), and tumor efficacy of telatinib combined with docetaxel (D). D was administered at a fixed dose of 75mg/m 2 on day 1 of 21-day cycles. Telatinib was administered orally, twice daily (bid) from day 3 of Cycle 1 and onwards, thereafter continuously. Dosing of telatinib commenced at 600mg bid (cohort 1, n=6) and increased to 900mg bid (cohort 2, n=7). PK in Cycle 1 were determined on day 1 (D) and day 21 (telatinib). In Cycle 2 comparative PK profiles for both telatinib and D were sampled on days 1–3. Results: Thirteen patients (pts) with advanced solid tumors were enrolled (9M/4F; median age: 56 [range: 34–69]; ECOG PS 0/1: 3/10). A total of 69 cycles have been completed (range,1–10). Treatment-emergent adverse events of CTCAE =3 (NCI-CTC v3.0) were neutropenia (n=11, 79%), fever (n=2, 15%), and fatigue (n=2, 11%). Adverse events of CTC =3 occuring in two pts was febrile neutropenia. Others occurring in only one patient were; hypertension, ALT increase, dehydration, and reversible symptomatic pneumonitis. Study treatment-related adverse events leading to a dose reduction or interruption were neutropenia (n=5, 38%), hypertension (n=1), ALT increase (n=1), and fatigue (n=1). Two pts with prostate ca and 1 with cervical ca had a confirmed partial response. Five pts (1 NSCLC, 1 esophageal ca, 1 renal cell ca and 2 prostate ca) had stable disease for =4 cycles. Mean AUC of D increased by 48% in cohort 1, but only by 16% in cohort 2. Thus, PK data to date do not indicate a clear clinically relevant interaction between telatinib and D. Conclusions: The combination of telatinib and D was tolerated without reaching the toxic dose at telatinib 900mg bid and D 75mg/m 2 . This combination has demonstrated promising antitumor activity. An extension of the cohort at 900mg bid with 75mg/m 2 D is being evaluated to gain further safety and PK data. No significant financial relationships to disclose.
Inhaled antibiotic treatment. Tolerance, compliance and quality of life
Authors: Antonio Alvarez, Laura Ruano, Montserrat Vendrell, Rosa Giron, Mª Pilar Ausin, Miguel Angel Martínez, Marina Blanco, David de la Rosa, David Blanquer, Ines Herrero, Javier de Gracia
Journal: European Respiratory Journal (2011)

Multicenter, prospective, observational, analytical cohort study.   Objective:  To compare tolerance, quality of life and compliance in self-administration of antibiotics, by jet nebulizers or electronic devices.   Material and methods:  Adult patients with bronchiectasis (BQ) of any etiology, with chronic bronchial infection by  P. aeruginosa  following nebulized antibiotic treatment by a jet nebulizer and high flow compressor for at least two months before being included in the study. The selection of patients was carried out consecutively for outclinic patients diagnosed of bronchiectasis in every Respiratory Department participating in the study. Clinical data and respiratory function were recorded. Compliance, tolerance and quality of life questionnaires (St George and SF36) before and after every period of treatment were also requested. The data given by an electronic device in the electronic nebulizer giving doses information and drug administration periods were recorded.   Results:  Sixty eight patients (51% female, mean age 61±19, FEV1 57±20%) from 9 different Hospitals were included. Both devices showed no differences concerning preparation time and device cleaning, nor treatment adherence. However, the use of the electronic device significantly decreased nebulization time interlude (p   Conclusions:  Electronic nebulizers seem to be better tolerated, save time and improve the patient9s quality of life.