tbuckley/cabot-search huggingface dataset:
How Is Mechanical Ventilation Employed in the Intensive Care Unit?
Authors: ANDRÉS ESTEBAN, ANTONIO ANZUETO, INMACULADA ALÍA, FEDERICO GORDO, CARLOS APEZTEGUÍA, FERNANDO PÁLIZAS, DAVID CIDE, ROSANNE GOLDWASER, LUIS SOTO, GUILLERMO BUGEDO, CARLOS RODRIGO, JORGE PIMENTEL, GUILLERMO RAIMONDI, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

A 1-d point-prevalence study was performed with the aim of describing the characteristics of conventional mechanical ventilation in intensive care units ICUs from North America, South America, Spain, and Portugal. The study involved 412 medical-surgical ICUs and 1,638 patients receiving mechanical ventilation at the moment of the study. The main outcome measures were characterization of the indications for initiation of mechanical ventilation, the artificial airways used to deliver mechanical ventilation, the ventilator modes and settings, and the methods of weaning. The median age of the study patients was 61 yr, and the median duration of mechanical ventilation at the time of the study was 7 d. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic obstructive pulmonary disease (13%), coma (10%), and neuromuscular disorders (10%). Mechanical ventilation was delivered via an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1%. Ventilator modes consisted of assist/control ventilation in 47% of patients and 46% were ventilated with synchronized intermittent mandatory ventilation, pressure support, or the combination of both. The median tidal volume setting was 9 ml/kg in patients receiving assist/control and the median setting of pressure support was 18 cm H2O. Positive end-expiratory pressure was not employed in 31% of patients. Method of weaning varied considerably from country to country, and even within a country several methods were in use. We conclude that the primary indications for mechanical ventilation and the ventilator settings were remarkably similar across countries, but the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country.
Combined endoscopic evaluation of the effectiveness of neoadjuvant chemotherapy of NSCLC using autofluorescence and spectroscopic methods
Authors: Yulia Kulakova, Andrey Arsenev, Evgeniy Levchenko, Alexey Barchuk, Andrey Akopov
Journal: European Respiratory Journal (2011)

Objectives:  To estimate the informativity of autofluorescence bronchoscopy and spectroscopy for evaluating the effectiveness of neoadjuvant chemotherapy (NCT) for lung cancer.   Material and methods:  The study included 46 patients with central NSCLC IIIa/IIIb stage who underwent 2-4 courses of platinum-based NCT. Endoscopy was done before treatment started and repeated each 21 day. Combined endoscopic investigation included: bronchoscopy in conventional mode (CB), spectroscopy in conventional mode (CS), bronchoscopy in autofluorescence mode (AFB) and spectroscopy in autofluorescence mode (AFS). Integrated system for autofluorescence and spectroscopy ClearVu Elite (Perceptronix Med. Inc., Canada) was used. The data obtained were compared with the results of histological study of biopsy samples from the respective sites.   Results:  The sensitivity and specificity of the combination of AFB and AFS was 97.1% and 88.3%, respectively vs. CB and CS - 66,7% and 86,9%, respectively. Combined endoscopy revealed that the NCT was effective in 41,3% cases (n = 19 - partial endoscopic response), in 4 patients (10,3%) endoscopic tumor progression was found. Endobronchial spread of the tumor in 30.4% of cases (p = 0.03) was defined more accurately by AFB and AFS in comparison with CB and CS, it was important for choosing a volume of further resection. In 97,1% of cases, the data AFB and AFS is fully consistent with the results of histological studies (p = 0,02).   Conclusions:  The combination of AFB and AFS is effective in determination of margins of central lung cancer spread and effectiveness of NCT.
Protection of Mice Against Gross Leukemia by Interfering Action of Nonleukemogenic C-Type Murine Viruses Inoculated Into Newborns&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Georges Barski, Jung Koo Youn
Journal: JNCI Journal of the National Cancer Institute (1971)

Two long-term in vitro clonal cell lines, designated N1 and CL9, both of C3H mouse origin, were found to be chronically infected with abundantly replicating C-type virus particles. This confirms previous data. Concomitantly, these lines always showed, by immunofluorescence, Gross leukemia virus (GY) type-specific, ceil-surface antigen. The virus material collected from the supernatant, after freezing and thawing of these cell cultures, when concentrated by ultracentrifugation and injected into newborn C3HeB/Fe mice, produced no leukemia or pathological symptoms. However, the same material interfered markedly with the leukemic process when inoculated into newborns 4–5 hours before challenge with highly leukemogenic passage-A GY. This interference was particularly striking with the material from N1 cultures: Almost 60% of the mice had no leukemia during the 180-day observation period, as compared with 11% in the controls. Latency and survival time were prolonged in the leukemic mice. No interferon-like activity was observed in the plasma of mice inoculated with the material from N1 cultures. On the other hand, leukemogenesis was not significantly inhibited in mice receiving an interferon inducer, polyinosinic-polycytidylic acid, before and after challenge with GY. Other mechanisms possibly involved in this phenomenon, such as receptor blocking and virus substitution, are discussed.
Drug‐induced allergic hepatitis develops in mice when myeloid‐derived suppressor cells are depleted prior to halothane treatment
Authors: Mala Chakraborty, Aaron M. Fullerton, Kenrick Semple, Lynette S. Chea, William R. Proctor, Mohammed Bourdi, David E. Kleiner, Xiangbin Zeng, Pauline M. Ryan, Pradeep K. Dagur, Julia D. Berkson, Timothy P. Reilly, Lance R. Pohl
Journal: Hepatology (2015)

Clinical evidence suggests that many cases of serious idiosyncratic drug‐induced liver injury are mediated by the adaptive immune system in response to hepatic drug‐protein adducts, also referred to as “drug‐induced allergic hepatitis”; but detailed mechanistic proof has remained elusive due to the lack of animal models. We have hypothesized that drug‐induced allergic hepatitis is as rare in animals as it is in humans due at least in part to the tolerogenic nature of the liver. We provide evidence that immune tolerance can be overcome in a murine model of halothane‐induced liver injury initiated by trifluoroacetylated protein adducts of halothane formed in the liver. Twenty‐four hours after female Balb/cJ mice were initially treated with halothane, perivenous necrosis and an infiltration of CD11b + Gr‐1 high cells were observed in the liver. Further study revealed a subpopulation of myeloid‐derived suppressor cells within the CD11b + Gr‐1 high cell fraction that inhibited the proliferation of both CD4 + and CD8 + T cells. When CD11b + Gr‐1 high cells were depleted from the liver with Gr‐1 antibody treatment, enhanced liver injury was observed at 9 days after halothane rechallenge. Toxicity was associated with increased serum levels of interleukin‐4 and immunoglobulins G1 and E directed against hepatic trifluoroacetylated protein adducts, as well as increased hepatic infiltration of eosinophils and CD4 + T cells, all features of an allergic reaction. When hepatic CD4 + T cells were depleted 5 days after halothane rechallenge, trifluoroacetylated protein adduct–specific serum immunoglobulin and hepatotoxicity were reduced. Conclusion : Our data provide a rational approach for developing animal models of drug‐induced allergic hepatitis mediated by the adaptive immune system and suggest that impaired liver tolerance may predispose patients to this disease. (H epatology 2015;62:546–557
Functional activities of human alveolar macrophages
Authors: G Velluti, O Capelli, L Richeldi, E Prandi, M Lega, E Rovatti, M Covi
Journal: European Respiratory Journal (1990)

activity was high in 8/10 patients but not conuols.When anti C5a antibody was 1 BAL fluid a significant inhibition chemowctic activity occurred (fig.2).support those of F' otJRNIER et al. [2].The acute response in HP is associated with neutrophils into the lungs, whilst the • chronic responses are associared with the nature of neuuophil chemotactic investigated the role of complement using Results showed that antibodies toward can diminish, without abolishing, chemotactic activity.These data agree with vn•oo m•.AWA et a{.(J) in patients With 3CUle and indicate that in BAL fluid of pa-' .
Peculiar properties of sleep structure and impact of antidepressive therapy in COPD patients with concomitant depressive episode
Authors: Liudmyla Iashyna, Yuri Feshchenko, Svitlana Moskalenko, Maryna Polianska, Olena Potochniak, Vladimir Kuts
Journal: European Respiratory Journal (2013)

Aim of study:   to study the influence of agomelatin on sleep stages in COPD patients with depressive episode (DE).    Materials and methods  : 11 COPD patients with clinically diagnosed by psychiatrist DE (PHQ-9 score > 15), 4 female and 7 male, mean age (66,9 ± 2,7) years received agomelatin 25 mg 1 hour before sleep OD during 3 month on the background of standard COPD therapy according severity. Patients were assessed with polysomnography (PSG) at baseline, 2 weeks and 3 month of studied treatment.    Results:   all patients initially had normal AHI (1,6 ± 0,3) per hour.  REM stage was abnormal at baseline - increased (31,4 ± 3,2)% of total sleep time (TST) vs normal duration of REM stage in healthy population (NINDS).  3 rd  and 4 th  sleep stages were significantly decreased at baseline (4,6 ± 7,1)% TST. After 2 weeks of therapy improvement of deep sleep stages was noted – (9,2 ± 2,0)% TST (p   Tendency to the improvement of REM stage was noted also after 2 weeks of treatment– it decreased to (27,5 ± 3,0)%, and after 3 month - to (24,9±4,0) of TST, p   Sleep efficacy increased from (65,0 ± 6,1) to (78,2 ± 3,2), p    Conclusion:   use of agomelatin in complex COPD therapy in patients with COPD and depressive episode improved sleep structure, that revealed in: tendency to the normalization of REM, deep sleep stages and sleep efficacy.
Effects of the Tumor-Promoting Agent 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol-13-acetate on Normal and “Preneoplastic” Mouse Submandibular Gland Epithelial Cells In Vitro
Authors: M A Knowles
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of the promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied on mixed primary cultures of C57BL/Icrf-at mouse submandibular gland and on slowly proliferating preneoplastic epithelial foci derived from such cultures. No cytologic alterations were noted in the TPA-treated epithelium. The development of three-dimensional epithelial ducts occurring between 30 and 60 days in vitro in untreated cultures was markedly inhibited in TPA-treated cultures. Epithelial proliferation, as shown by the [H]thymidine labelling index and mitotic index, seemded to increase during treatment with TPA and fall between the weekly treatments. Long-term TPA treatment increased the incidence of slow-growing foci in cultures previously treated with 7,12-dimethylbenz[a]anthracene but not in cultures treated with dimethyl sulfoxide. TPA had no effect on the emergence of tumorigenic cell lines at a late stage in culture or on the development of such lines from preexisting foci derived from non-TPA-treated cultures.
Characterisation of a new Daisy cell line representative of human alveolar macrophage (hAM)
Authors: Yvette Hayman, Simon Hart, Alyn Morice
Journal: European Respiratory Journal (2011)

Introduction:  Techniques used to obtain primary hAM are invasive, often providing low yields which cannot be expanded  in vitro.  No human cell line exists as an alternative. We characterised a new human cell line capable of expansion and spontaneous differentiation.   Methods:  Cells were cultured in RPMI1640 with 10% foetal bovine serum and penicillin/streptomycin (100U/ml;0.1mg/ml) in a humidified 5% CO 2  atmosphere, passaged every 2 days. Light and transmission electron microscopy comparing Daisy cells with THP-1 cells stimulated with phorbol myristate acetate (PMA;50μg/ml;24h) was performed. Flow cytometric immunophenotype studies were performed analysing CD 11b, 14, 16, 23, 24, 32, 36, 64, 163 and 206 expression. Results were compared with both THP-1 cells and primary hAM obtained by bronchoalveolar lavage. Phagocytic capability by zymosan uptake (mg/ml;1h), mycoplasma screening by fluorescence microscopy and opsonised antigen binding by flow cytometry were also assessed.   Results:  Microscopy showed Daisy cells to be similar in size, shape and granularity to PMA stimulated THP-1 cells with a higher proportion of heterochromatin, pseudopodia and vesicular inclusions. Daisy cells were shown to express lower levels of CD11b, 14 and 32 compared with PMA stimulated THP-1 cells yet higher levels of CD36, 80, 163 and 206. CD marker expression of Daisy cells more closely resembled that of primary hAM. Zymosan was readily phagocytosed, mycoplasma was not detected and high levels of opsonised antigen binding were seen in Daisy but not THP-1 cells.   Conclusions:  The new Daisy cell line shows characteristics of mature hAM yet can be maintained and cultured providing a useful tool in respiratory research.
The body mass index and chronic obstructive pulmonary disease in the BOLD study
Authors: Lowie Vanfleteren, Bernd Lamprecht, Emiel Wouters, Louisa Gnatiuc, Peter Burney, Michael Studnicka, Frits Franssen
Journal: European Respiratory Journal (2013)

Background:  Nutritional status is related to clinical outcome and prognosis in patients with COPD. However, the relation between the body mass index (BMI) and COPD has not been studied in the general population.   Aims:  To assess the relation between BMI and presence and severity of COPD in a general worldwide population, taking into account confounding factors.   Methods:  13.774 participants (49% male, 23% current smokers, mean age: 56±11 years, mean BMI: 26.6±5.4kg/m2) in the Burden of Obstructive Lung Disease initiative were included. COPD was defined spirometrically as post-bronchodilator FEV 1 /FVC 1 >80%), stage 2 (FEV 1  50-80%) and stage 3+ (FEV 1  2 , obese BMI as >30 kg/m 2 .   Results : Subjects were gradually more distributed towards a lower BMI with increase in COPD severity. (Figure) Odds ratios for low BMI (adjusted for age, gender and smoking) gradually increased with COPD stage compared to normal lung function (NLF) (1.4 (1.1-1.7); 2.0 (1.6-2.5); 5.0 (3.7-6.7) for stage 1, 2 and 3+ resp.). The adjusted odds for obesity were generally lower in COPD compared to NLF, although the odds were comparable in stage 2 COPD. (0.6 (0.5-0.8); 1.0 (0.8-1.2); 0.6 (0.4-0.9) for stage 1, 2 and 3+ resp.)   Conclusion:   In a general worldwide population the presence and severity of COPD is associated with a lower BMI. Although subjects with moderate COPD have equal odds for obesity.
CD99: An endothelial passport for leukocytes
Authors: Michael J. Hickey
Journal: The Journal of Experimental Medicine (2015)

Macrophages are critically important for the regulation of tumor growth and metastases.They contribute to tumor angiogenesis, tumor cell extravasation, and survival at the sites of metastases.Now, Kitamura et al., using mouse models of breast cancer, have uncovered a major role for a CCL2-induced chemokine cascade that supports macrophage recruitment and retention in metastatic sites in the lung.Macrophages found in metastatic sites have a distinct phenotype and are referred to as metastasis-associated macrophages (MAMs).Similar to other tumor-associated macrophages, MAMs originate from circulating inflammatory monocytes, which are recruited to the tumor site in response to the chemokine CCL2.This raised the attractive possibility of controlling metastasis by targeting CCL2.However, an anti-CCL2 antibody was found to be ineffective in humans.Furthermore, loss of CCL2 signaling reduced the numbers of circulating monocytes, leading to an increased susceptibility to infection in mouse models.This necessitated the search for more precise mechanisms regulating MAM migration, as addressed by Kitamura et al. in the current study.Kitamura et al. found that MAMs expressed the CCL2 receptor CCR2, and activation of CCR2 signaling prompted MAMs to secrete another chemokine, CCL3.The increased CCL3 secretion resulted in enhanced MAM-cancer cell interaction, at least in part through integrin a4, and prolonged the retention of MAMs in the metastatic sites, resulting in extravasation of cancer cells.The authors implicated the CCL3 receptor CCR1 on MAMs as the main mechanism responsible for CCL3-mediated retention of MAMs in metastatic sites.This study identifies a novel prometastatic chemokine cascade that promotes lung metastasis in breast cancer.Although the concept of chemokine crosstalk has been described previously, this work demonstrates, for the first time, the existence of the CCL2-CCL3 cascade in vivo and its contribution to tumor metastases.It appears that CCL2 is primarily responsible for macrophage migration, whereas CCL3 is primarily responsible for macrophage retention.It also seems likely that CCL2-induced CCL3 expression is specific to the prometastatic macrophage, which raises the exciting possibility of more effective identification and targeting of MAMs.However, the molecular mechanism by which CCL3 activates macrophages and promotes their interaction with tumor cells needs to be elucidated.CCL3 is known to have potent effects on neutrophil extravasation and activation.Although neutrophils may not play a major role in the breast tumor models used in this study, the potential involvement of neutrophils in other models and in patients requires further analysis.This study presents a more refined picture of the role of macrophages in metastases than has been appreciated to date, and it suggests that more precise targeting of macrophages may allow us to curtail the development of metastases.
The mutational landscape of hepatocellular carcinoma
Authors: Ju-Seog Lee
Journal: Clinical and Molecular Hepatology (2015)

The development of hepatocellular carcinoma (HCC) is a complex process, and HCC arises from the accumulation of multiple genetic alterations leading to changes in the genomic landscape. Current advances in genomic technologies have revolutionized the search for genetic alterations in cancer genomes. Recent studies in which all coding exons in HCC were sequenced have shed new light on the genomic landscape of this malignant disease. Catalogues of these somatic mutations and systematic analysis of catalogued mutations will lead us to uncover candidate HCC driver genes, although further functional validation is needed to determine whether these genes play a causal role in the development of HCC. This review provides an overview of previously known oncogenes and new oncogene candidates in HCC that were uncovered from recent exome or whole-genome sequencing studies. This knowledge provides direction for future personalized treatment approaches for patients with HCC. Keywords: Hepatocellular carcinoma; Cancer genomics; Somatic mutations; TERT; TP53
Abstract 15466: Echo Assessment of Ventricular Stiffness Based on Epicardial Movement: Insights from Analysis of Changes after Antihypertensive Treatment in the Untreated Hypertensive Patients
Authors: Misato Otsuka, Akiko Goda, Mitsuru Masaki, Chikako Yoshida, Ayumi Nakaboh, Akiyo Eguchi, Yoshiro Naito, Shinichi Hirotani, Masaaki Lee-Kawabata, Tohru Masuyama
Journal: Circulation (2010)

Background: Left ventricular (LV) epicardial movement reflects LV stiffness, and its M-mode echo quantitation is likely to provide an estimate of LV stiffness. Specifically, diastolic wall strain (...
Polypoid Spitz naevus: the benign counterpart of polypoid malignant melanoma
Authors: G. Fabrizi, G. Massi
Journal: British Journal of Dermatology (2000)

Polypoid malignant melanoma is a peculiar morphological variant of melanoma with a distinct exophytic pattern of growth. This form of melanoma is usually very thick and the prognosis is accordingly poor. We present here a previously undescribed form of Spitz naevus which had a similar polypoid exophytic silhouette and marked cytological atypia. Despite these close morphological similarities, polypoid Spitz naevus evolves in a completely benign manner. Morphologically, polypoid Spitz naevus can be distinguished from polypoid melanoma by the absence of mitoses and by the prominent stromal reaction throughout the lesion.
One-Stage Off-Pump Transapical Mitral Valve Repair and Aortic Valve Replacement
Authors: Gino Gerosa, Augusto D’Onofrio, Erica Manzan, Laura Besola, Eleonora Bizzotto, Fabio Zucchetta, Giuseppe Tarantini, Demetrio Pittarello, Andrea Colli
Journal: Circulation (2015)
Characterising patterns of prescribing for UK COPD patients with comorbidities or history of pneumonia
Authors: David Price, Katsiaryna Bichel, Daniel West, Victoria Carter, Valerie L. Ashton, Rebecca Stewart
Journal: European Respiratory Journal (2014)

Background : High doses of inhaled corticosteroids (ICS) can increase risk of type 2 diabetes, osteoporosis and pneumonia (Price, D.  et al.  Prim Care Respir J  2013; 22:92-100).   Aim : To characterise prescribing patterns for UK COPD patients with comorbidities or history of pneumonia commencing first maintenance therapy for COPD.   Methods : Retrospective observational study, using Optimum Patient Care Research Database, of patients prescribed first maintenance therapy for COPD (ICS, long-acting β agonist [LABA], long-acting muscarinic antagonist [LAMA] or combination) in 2009-2012 at or after COPD diagnosis confirmed by spirometry. Study period was 1 year before and 1-3 years after prescription for therapy. Therapy, comorbidities and history of pneumonia were recorded.   Results : Of 2217 patients (55% male; 45% smokers; 47% ex-smokers; 22% aged ‹60 years; 54% 60-75 years; 24% ≥75 years) 24%, 11%, 7% and 17% had, at any time, diabetes and/or therapy, osteoporosis, history of pneumonia and asthma, respectively.   Conclusion : ICSs and their combinations are prescribed frequently for COPD patients with diabetes, osteoporosis and history of pneumonia, who might be more at risk of ICS side effects, while bronchodilator monotherapy is prescribed frequently for COPD patients with asthma who might benefit from added ICS.