tbuckley/cabot-search huggingface dataset:
Pre–B-Cell Colony-enhancing Factor as a Potential Novel Biomarker in Acute Lung Injury
Authors: Shui Q. Ye, Brett A. Simon, James P. Maloney, April Zambelli-Weiner, Li Gao, Audrey Grant, R. Blaine Easley, Bryan J. McVerry, Rubin M. Tuder, Theodore Standiford, Roy G. Brower, Kathleen C. Barnes, Joe G. N. Garcia
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.
"Education is the passport to the future": enabling today's medical teachers to prepare tomorrow's respiratory health practitioners
Authors: Sharon Mitchell, Konrad E. Bloch, Indre Butiene, Brendan G. Cooper, Irene Steenbruggen, Alanna Hare, Konstantinos Kostikas, Ian M. Adcock, James Paton, Monica Fletcher, Robin Stevenson, Gernot Rohde, Anita K. Simonds
Journal: European Respiratory Journal (2014)

“ If we are to achieve results never before accomplished, we must expect to employ methods never before attempted ”

Sir Francis Bacon 1561–1626.

British aviators Alcock and Brown made the first transatlantic flight in 1919 – In 2013, the total number of flights in Europe was 9.5 million. 

In July 1969, Apollo 11 Commander Neil Armstrong landed on the moon – today you can book your flight to space online with Virgin Galactic. 

Throughout the 1990s, medical education was transformed as a direct consequence of more complex patient needs and the reorganisation of healthcare delivery. Medical education refers to the educational process required to prepare the medical professional for entry into practice as well as provision of educational activities for lifelong learning. This educational process is aimed at physicians, nurses, technicians, physiotherapists, scientists and other related professions who deliver care to the patient and public. Today’s medical professional is bound by demanding healthcare systems [1–3], internationalisation of localised diseases [4], shorter more intense training periods and dependence on medical technology [5].

Global funds, trade and networks are all examples of initiatives that demonstrate our entry into an international, mobile era. In 1993, the European Council (EU) council directive 93/16 stipulated that those EU nationals holding an EU primary or specialist medical qualification were to be allowed to practice within any EU country [6]. We are aware that many European countries are heavily reliant on foreign-trained medical staff to support their medical systems [7]. Patient tourism has also warranted attention [8], as more and more patients opt to cross international borders in search of treatment.

The European Respiratory Society (ERS) International Congress welcomes respiratory health professionals from all over the world. As a provider of continuous …
Carcinogenicity of Different Polycyclic Hydrocarbons in the Respiratory Tract of Hamsters&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: A Sellakumar, P Shubik
Journal: JNCI Journal of the National Cancer Institute (1974)

The respiratory tracts of male Syrian hamsters were exposed to different polycyclic hydrocarbons: benz [a]anthracene, [benzo[b]fluoranthene, dibenz[a,h]-anthracene, dibenzoa,i]pyrene (DB[a,i]P), and pyrene. The carcinogens were given by multiple intratracheal instillations at two dose levels with an equal amount of ferric oxide in saline. Except for DB [a,i]P, most compounds were not carcinogenic in the respiratory tract at the dose levels given. Both groups that received DB[a,i]P had a high incidence of carcinomas. In the hamsters treated with the lower dose (8 mg), 16 of 34 (47%) developed respiratory tract tumors, and in those receiving the higher dose (12 mg), 39 of 44 (89%) developed respiratory tract tumors. In the latter group, more than 50% of the tumors were squamous cell carcinomas, with the first tumor seen at the 27th week. Most tumors in both groups arose from the epithelium of the bronchi and trachea. The present results demonstrate that DB[a,i]P is a more potent carcinogen in the respiratory tract than benzo[a]pyrene. The other carcinogens, effective in other organs such as skin, showed little effect in the respiratory tract.
A trial of oral delta-1-(trans)-tetrahydrocannabinol in reversible airways obstruction.
Authors: B H Davies, S Radcliffe, A Seaton, J D Graham
Journal: Thorax (1975)

Sixteen patients with proven reversible airways obstruction were admitted to a double-blind study to compare the bronchodilator effects of oral delta-1-(trans)-tetrahydrocannabinol (delta-1-THC) and salbutamol. Measurements of forced vital capacity, forced expired volume in one second, peak expiratory flow rate, and maximum expiratory flow rate at 50 percent vital capacity after 10 mg oral delta-1-THC did not differ significantly from the effect of placebo, whereas increases after salbutamol were significant. Analyses of mood, pulse rate, blood pressure, and electrocardiogram showed no important changes after oral delta-1-THC. In vitro studies with isolated tracheal muscle indicate that the activity of delta-1-THC is 1,000 times less than the equivalent dose of isoprenaline, and the effect of delta-1-THC is not abolished by beta-adrenoreceptor blocking agents. It is concluded that oral delta-1-THC, at a dose of 10 mg, does not produce clinically significant bronchodilatation in patients with reversible airways obstruction.
Survey of bronchoscope disinfection practices by chest physicians attending IP CME in Navi Mumbai, Maharastra
Authors: H.S. Sandeep, Arvind Kate, Parag Chaudhari, Prashant Chhajed
Journal: European Respiratory Journal (2012)

Aim:  To study various methods used for disinfecting bronchoscope by delegates attending a CME on Interventional Pulmonology.  Methods:  A 25 question survey was divided into sub groups like location of bronchoscopy suite, disinfecting techniques, bronchoscope care and sedation practices. The survey was distributed to participants from Western India in a CME on Interventional Pulmonology.  Results: 31 out of 40 participants completed the questionnaire. One was excluded from the study as it was incomplete. 8 questionnaires were completed by medical director of bronchoscopy suite, 18 by chest physicians and 5 by the fellows.  Conclusion: Increased awareness and education is required for Bronchoscopy disinfection techniques and adherence to guidelines.
Manipulation of Death Pathways in Desmin-Related Cardiomyopathy
Authors: Alina Maloyan, Jennifer Sayegh, Hanna Osinska, Balvin H.L. Chua, Jeffrey Robbins
Journal: Circulation Research (2010)

Rationale : Transgenic mice with cardiac specific overexpression of mutated αB-crystallin (CryAB R120G ) display Desmin-related myopathy (DRM) with dilated cardiomyopathy and heart failure. Our previous studies showed the presence of progressive mitochondrial abnormalities and activation of apoptotic cell death in CryAB R120G transgenic hearts. However, the role of mitochondrial dysfunction and apoptosis in the overall course of the disease was unclear. Objective : We tested the hypothesis that prevention of apoptosis would ameliorate CryAB R120G pathology and decrease morbidity. Methods and Results : We crossed CryAB R120G mice to transgenic mice with cardiac specific overexpression of Bcl-2. Sustained Bcl-2 overexpression in CryAB R120G hearts prolonged CryAB R120G transgenic mice survival by 20%. This was associated with decreased mitochondrial abnormalities, restoration of cardiac function, prevention of cardiac hypertrophy, and attenuation of apoptosis. CryAB R120G misfolded protein aggregation was significantly reduced in the double transgenic. However, inhibition of apoptotic signaling resulted in the upregulation of autophagy and alternative death pathways, the net result being increased necrosis. Conclusion : Although Bcl-2 overexpression prolonged life in this DRM model, in the absence of apoptosis, another death pathway was activated.
Effect of Ultrafiltration on Thermal Variables, Skin Temperature, Skin Blood Flow, and Energy Expenditure during Ultrapure Hemodialysis
Authors: Frank M. van der Sande, Laura M. Rosales, Zohar Brener, Jeroen P. Kooman, Martin Kuhlmann, Garry Handelman, Roger N. Greenwood, Mary Carter, Daniel Schneditz, Karel M. Leunissen, Nathan W. Levin
Journal: Journal of the American Society of Nephrology (2005)

The cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.
Gene Expression Profiles Predict Early Relapse in Ovarian Cancer after Platinum-Paclitaxel Chemotherapy
Authors: Lynn C. Hartmann, Karen H. Lu, Gerald P. Linette, William A. Cliby, Kimberly R. Kalli, David Gershenson, Robert C. Bast, James Stec, Natalia Iartchouk, David I. Smith, Jeffrey S. Ross, Sebastian Hoersch, Viji Shridhar, James Lillie, Scott H. Kaufmann, Edwin A. Clark, Andrew I. Damokosh
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only ∼20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy. Experimental Design: To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes. Supervised learning algorithms were applied in an effort to develop a binary classifier that could discriminate women at risk for early (≤21 months) versus late (&amp;gt;21 months) relapse after initial chemotherapy. Results: A 14-gene predictive model was developed using a set of training samples (n = 51) and subsequently tested using an independent set of test samples (n = 28). This model correctly predicted the outcome of 24 of the 28 test samples (86% accuracy) with 95% positive predictive value for early relapse. Conclusions: Predictive markers for early recurrence can be identified for platinum-paclitaxel combination chemotherapy in primary ovarian carcinoma. The proposed 14-gene model requires further validation.
Nitroprusside in Critically Ill Patients with Left Ventricular Dysfunction and Aortic Stenosis
Authors: Umesh N. Khot, Gian M. Novaro, Zoran B. Popović, Roger M. Mills, James D. Thomas, E. Murat Tuzcu, Donald Hammer, Steven E. Nissen, Gary S. Francis
Journal: New England Journal of Medicine (2003)

Vasodilators are considered to be contraindicated in patients with severe aortic stenosis because of concern that they may precipitate life-threatening hypotension. However, vasodilators such as nitroprusside may improve myocardial performance if peripheral vasoconstriction is contributing to afterload.We determined the response to intravenous nitroprusside in 25 patients with severe aortic stenosis and left ventricular systolic dysfunction. Patients were included in the study if they had been admitted to the intensive care unit for invasive hemodynamic monitoring of heart failure and if they had a depressed ejection fraction (<or=0.35), severe aortic stenosis (aortic-valve area, <or=1 cm2), and a depressed cardiac index (<or=2.2 liters per minute per square meter). Patients were excluded if they had hypotension, defined as either the need for intravenous inotropic or pressor agents or a low mean systemic arterial pressure (<60 mm Hg). Patients were enrolled irrespective of other, coexisting valve disease or coronary artery disease.At base line, the mean (+/-SD) ejection fraction was 0.21+/-0.08; the aortic-valve area was 0.6+/-0.2 cm2, with peak and mean gradients of 65+/-37 and 39+/-23 mm Hg, respectively; and the cardiac index was 1.60+/-0.35 liters per minute per square meter. After six hours of therapy with nitroprusside (at which time the dose had been increased to a mean of 103+/-67 microg per minute), the cardiac index had increased to 2.22+/-0.44 liters per minute per square meter (P<0.001 for the comparison with base line). After 24 hours of nitroprusside infusion (dose, 128+/-96 microg per minute), the cardiac index had increased further, to 2.52+/-0.55 liters per minute per square meter (P<0.001 for the comparison with base line). Nitroprusside was well tolerated and had minimal side effects.Nitroprusside rapidly and markedly improves cardiac function in patients with decompensated heart failure due to severe left ventricular systolic dysfunction and severe aortic stenosis. It provides a safe and effective bridge to aortic-valve replacement or oral vasodilator therapy in these critically ill patients.
Genetic influences in gastro-oesophageal reflux disease: a twin study
Authors: I Mohammed
Journal: Gut (2003)

<b>Background:</b> A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD. <b>Aims:</b> To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins. <b>Methods:</b> A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year. <b>Results:</b> Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19–81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20–82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% <i>v</i> 26%; p&lt;0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32–55%) of the variance in liability to GORD is due to additive genetic factors. <b>Conclusions:</b> There is a substantial genetic contribution to the aetiology of GORD.
Cylindromatosis gene CYLD regulates hepatocyte growth factor expression in hepatic stellate cells through interaction with histone deacetylase 7
Authors: Rajeswara R. Pannem, Christoph Dorn, Claus Hellerbrand, Ramin Massoumi
Journal: Hepatology (2014)

Hepatic fibrosis is considered as a physiological wound-healing response to liver injury. The process involves several factors, such as hepatocyte growth factor (HGF), which restrains hepatic injury and facilitates reversibility of fibrotic reaction in response to an acute insult. Chronic liver injury and sustained inflammation cause progressive fibrosis and, ultimately, organ dysfunction. The mechanisms tipping the balance from restoration to progressive liver tissue scarring are not well understood. In the present study, we identify a mechanism in which the tumor-suppressor gene, cylindromatosis (CYLD), confers protection from hepatocellular injury and fibrosis. Mice lacking CYLD (CYLD −/− ) were highly susceptible to hepatocellular damage, inflammation, and fibrosis and revealed significantly lower hepatic HGF levels, compared to wild-type (WT) animals. Exogenous application of HGF rescued the liver injury phenotype of CYLD −/− mice. In the absence of CYLD, gene transcription of HGF in hepatic stellate cells was repressed through binding of histone deacetylase 7 (HDAC7) to the promoter of HGF. In WT cells, CYLD removed HDAC7 from the HGF promoter and induced HGF expression. Of note, this interaction occurred independently of the deubiquitinating activity of CYLD. Conclusions : Our findings highlight a novel link between CYLD and HDAC7, offering mechanistic insight into the contribution of these proteins to progression of liver disease. Thus, through regulation of HGF level, CYLD ameliorates hepatocellular damage and liver fibrogenesis. (Hepatology 2014;60:1066–1081)
Could the neural ABC explain the mind?
Authors: Maurice K. D. Schouten, Huib Looren de Jong
Journal: Behavioral and Brain Sciences (2004)

Gold & Stoljar are right in rejecting the radical neuron doctrine, but we argue that their distinction between determination and explanation is not principled enough to support their conclusion. We claim that the notions of multiple supervenience and screening-off offer a more precise construal of the dissociation between explanation and determination that lies at the heart of the antireductionist position.
New Strategies in the Molecular Targeting of Glioblastoma: How Do You Hit a Moving Target?
Authors: Timothy F. Cloughesy, Paul S. Mischel
Journal: Clinical Cancer Research (2011)

Cancer is a molecularly complex, genomically unstable disease. Selection for drug-resistant mutations, activation of feedback loops, and upregulation of cross-talk pathways provide escape routes by which cancer cells maintain signal flux through critical downstream effectors to promote therapeutic resistance. Attempts to target signal transduction pathways in cancer may therefore require investigators to aim at a moving target. We need to anticipate the routes of resistance to guide the selection of drugs that will lead to durable therapeutic response. In this New Strategies article, we discuss the challenges imposed by the complexity and adaptive capacity of cancer and suggest potential new diagnostic strategies to more effectively guide targeted cancer therapy. We focus on glioblastoma, the most common malignant primary brain tumor of adults. Glioblastoma is a model for a pathway-driven, molecularly heterogeneous cancer for which new genomic insights obtained through The Cancer Genome Atlas are ripe for integration with functional biology and incorporation into new molecular diagnostic assays.
Chest wall mechanics during induction of anesthesia
Authors: Ilaria Milesi, Emanuela Zannin, Peter Kostic, Chiara Veneroni, Antonio Pedotti, Raffaele Dellacà, Peter Frykholm
Journal: European Respiratory Journal (2012)

BACKGROUND: It has been reported that anesthesia may be associated to variation in chest wall (CW) mechanics. We have developed a CW scanning system (CWSS) based on self-mixing laser interferometers that allows the measure of relative displacement. If this approach is combined with Forced Oscillation Technique (FOT) it allows to infer CW mechanics.  METHODS: Five patients were studied during anesthesia induction at different stages, while they were submitted to a sinusoidal pressure forcing at the mouth with components at 5, 11 and 19 Hz. At each step FRC (GE; Engstrom CareStation) and CW mechanics (phase displacement among these points and the pressure stimulus) were estimated by spectral technique.  RESULTS: figure 1 shows results at 11 Hz. At all steps rib cage and abdomen the pressure stimulus travels faster in the rib cage than in the abdomen, likely because of the high inertia of the latter. FRC presents a minimum during sedation, then it increased during pressure support and it reaches physiological values after the recruitment maneuver. The marked variation in φ induced by sedation on the lower rib cage may be related to the reduction in FRC.
Early Hyperglycemia Detected by Continuous Glucose Monitoring in Children at Risk for Type 1 Diabetes
Authors: Andrea K. Steck, Fran Dong, Iman Taki, Michelle Hoffman, Georgeanna J. Klingensmith, Marian J. Rewers
Journal: Diabetes Care (2014)

OBJECTIVE We explore continuous glucose monitoring (CGM) as a new approach to defining early hyperglycemia and diagnosing type 1 diabetes in children with positive islet autoantibodies (Ab+). RESEARCH DESIGN AND METHODS Fourteen Ab+ children, free of signs or symptoms of diabetes, and nine antibody-negative (Ab−) subjects, followed by the Diabetes Autoimmunity Study in the Young, were asked to wear a Dexcom SEVEN CGM. RESULTS The Ab+ subjects showed more hyperglycemia, with 18% time spent above 140 mg/dL, compared with 9% in Ab− subjects (P = 0.04). Their average maximum daytime glucose value was higher, and they had increased glycemic variability. The mean HbA1c in the Ab+ subjects was 5.5% (37 mmol/mol). Among Ab+ subjects, ≥18–20% CGM time spent above 140 mg/dL seems to predict progression to diabetes. CONCLUSIONS CGM can detect early hyperglycemia in Ab+ children who are at high risk for progression to diabetes. Proposed CGM predictors of progression to diabetes require further validation.