tbuckley/cabot-search huggingface dataset:
Abstract 15694: Absence of ECM Remodeling in Smad3 Mutant Mice Leads to Aggressive and Accelerated Aneurysmal Growth Through Distorted Downstream TGF-β Signaling
Authors: Ingrid van der Pluijm, Nicole van Vliet, Luna Buijs-Offerman, Aida Bertoli-Avella, Jeroen Essers
Journal: Circulation (2014)

Aneurysm-osteoarthritis syndrome (AOS), caused by  SMAD3  gene mutations, is an autosomal dominant condition characterized by aortic aneurysms and early-onset osteoarthritis. As part of the transcription factor complex Smad2/3/4, Smad3 is essential for TGFβ-activated downstream transcription of CTGF, MMPs, SMAD7 and others.  Smad3 -/-   mice show aneurysmal development at young age, but the underlying mechanism is unknown. To better understand the processes involved, we performed thorough phenotypic and molecular analyses of aneurysmal growth in  Smad3 -/-   mice. First, echocardiograms of cross-sectional studies in  Smad3 -/-   mice showed a significant increase in diameter of root and ascending aorta (18-20%), and significant increased aortic length (16-20%) already at 6 weeks of age, but no difference in aortic distensibility. Importantly, 50% of  Smad3 -/-   mice died suddenly between age 6-24 weeks. Successive macroscopic analysis showed up to a 5-fold increase in aortic diameter of the ascending aorta. Next, longitudinal studies showed a steep increase of aneurysmal growth within only 6 weeks. As the aneurysmatic aortic wall remained translucent, this was indicative for the absence of large scale extracellular matrix remodeling or collagen deposition. Indeed, immunohistochemistry showed a disturbed vascular wall and major sites without elastin or collagen. In accordance,  in vivo  molecular imaging showed increased aortic neutrophil elastase activity. Remarkably, CT-scans showed dilatations of the arterial tree at different sites of the body, as in AOS patients. In absence of Smad3, we still observed increased nuclear translocation of its co-transcription factor (p)Smad2, and upregulated pERK signaling, inferring increased upstream TGFβ signaling. Hence we reasoned that  Smad3  deficiency results in activated TGFβ signaling due to inability to activate downstream Smad7 transcription, a potent inhibitor of TGFβ signaling. Indeed, downstream TGFβ signaling seemed abolished as derived from the absence of MMP activation in  Smad3 -/-   mouse aortas. Identifying the underlying molecular mechanism due to Smad3 mutations is crucial to provide the correct ‘personalized’ treatment for aneurysmal disease.
The British Society of Gastroenterology
Authors: C Stanciu, J R Bennett
Journal: Gut (1972)

The scientific spring meeting was held at the Royal College of Physicians, London, on 10 March 1972.The morning was devoted to a symposium on 'Drug absorption and metabolism' when papers were read on 'Uptake from the intestinal lumen' (J.Nimmo), 'Mucosal transit' (D. Davis 'Kinetics of transport into blood in health and disease' (A.Brekenridge), 'Role of hepatic carrier proteins' (J.Levi), 'Aepatic metabolism' (R
Gene expression changes of Wnt signalling components during alveolar epithelial transdifferentiation
Authors: Domokos Bartis, Vijay K. D'Souza, Qian Wang, David R. Thickett
Journal: European Respiratory Journal (2014)

Type II alveolar epithelial cells (ATIIs) show clonal proliferation upon alveolar injury. During physiological healing transdifferentiation (TD) into Type I alveolar epithelial cells (ATIs) follows. On the contrary, pathological healing comprises tissue remodelling and fibrosis in chronic diseases of the lung. We aimed to identify Wnt ligands and Frizzled (Fzd) receptors which are involved in ATII→ATI TD. To examine spontaneous in vitro TD, we cultured human primary ATII cells isolated from lobectomy patients with normal lung function (n=11) for 3 and 6 days and processed cells for an Affimetrix microarray. Data analysis showed that more than 30% of significant (p<0.01) gene expression changes involved the Wnt signalling pathway. We selected Wnt4, Wnt5a, Wnt7a ligands and Fzd1, 2, 4, 5 and 7 receptors for further analysis to confirm gene expression changes using real-time qPCR. To compare data from in vitro cultured cells to freshly isolated cells, we FACS-sorted ATII-like and ATI-like cells from enzymatically digested human lung tissue based on EpCAM and CD208 or T1a/PDPN expression, respectively (n=12). Our qPCR data indicate that Wnt4, Wnt5a, Wnt7a expression is significantly (p<0.05) lower and Fzd2 is significantly higher in ATII-like cells than in ATI-like cells. Understanding ATII→ATI TD is a priority in revealing the molecular background of alveolar epithelial repair. Our microarray data indicate that Wnt signalling is particularly active during this process. Identification the components of Wnt signalling involved in the transdifferentiation process is the first step to mark molecular targets of future therapies.
Relation of Particle Dimension to Carcinogenicity in Amphibole Asbestoses and Other Fibrous Minerals&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M F Stanton, M Layard, A Tegeris, E Miller, M May, E Morgan, A Smith
Journal: JNCI Journal of the National Cancer Institute (1981)

Relation of Particle Dimension to Carcinogenicity in Amphibole Asbestoses and Other Fibrous Minerals Get access Mearl F. Stanton, Mearl F. Stanton Search for other works by this author on: Oxford Academic PubMed Google Scholar Maxwell Layard, Maxwell Layard 6 6Address reprint requests to Dr. Layard at his present address: Veterans Administration Medical Center, 3801 Miranda Ave., Palo Alto, Calif. 94304. Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrew Tegeris, Andrew Tegeris Search for other works by this author on: Oxford Academic PubMed Google Scholar Eliza Miller, Eliza Miller Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret May, Margaret May Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth Morgan, Elizabeth Morgan Search for other works by this author on: Oxford Academic PubMed Google Scholar Alroy Smith Alroy Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 5, November 1981, Pages 965–975, https://doi.org/10.1093/jnci/67.5.965 Published: 01 November 1981 Article history Received: 13 November 1980 Revision received: 06 May 1981 Accepted: 08 June 1981 Published: 01 November 1981
LSC 2013 abstract - Defining the bacterial microbiota of adult non-CF bronchiectasis
Authors: Geraint Rogers, Christopher van der Gast, Kenneth Bruce, David Serisier
Journal: European Respiratory Journal (2013)

Background: Despite its prevalence and contribution to morbidity, the microbiology of non-CF bronchiectasis is poorly defined. We present an in depth, cross-sectional, analysis of the bacteria present in the lower airways in this condition.

Methods: Paired induced sputum and bronchoalveolar lavage samples were obtained from 42 adult non-CF bronchiectasis patients and 16 healthy individuals. The bacterial species in these samples were detailed by 16S rRNA gene pyrosequencing, with meta-analysis use to distinguish 'core' and 'satellite' populations.

Results: Over 140 bacterial species were identified, including those associated with respiratory tract and opportunistic infections. Detected species included many that would be unlikely to be reported through standard diagnostic surveillance, such as those requiring anaerobic conditions for growth. Substantial species overlap was observed for paired samples. A core group of species, detected frequently and in high abundance, was defined. Within this group, Haemophilus influenzae made the greatest contribution to non-CF bronchiectasis sample similarity, though a range of respiratory pathogens and oral cavity species were also detected. A relatively small group of rare and low abundance satellite species were identified. The comparative contribution of core and satellite groups suggests a low level of random species acquisition.

Conclusions: This study has shown a complex and defined bacterial microbiota is present in non-CF bronchiectasis that is distinct from other respiratory contexts, and provides a basis for further investigations into the potential contribution of these bacteria to disease.
EmPHasis-10 is associated with clinical outcome measures in pulmonary hypertension
Authors: Janelle Yorke, Iain Armstrong, Carl Harries
Journal: European Respiratory Journal (2013)

Introduction: em PH asis-10 is a newly validated outcome measure for assessing health status in pulmonary hypertension (PH). It consists of 10 items on a semantic differential six-point scale (0–5); scaling range 0-50, higher scores representing worse health status. This study examines the relationship between em PH asis-10 and relevant clinical measures of disease severity and impact.

Methods: 225 patients (mean age 59±1; 69% female) with PH (39% idiopathic, congenital 21%, connective tissue 19%, other 21%), completed em PH asis-10, Hospital Anxiety and Depression Scale (HAD), Dyspnoea-12 (D-12), WHO Functional Class (FC) and six-minute walk distance (6MWD). We examined the ability of emPHasis-10 to distinguish subgroups of PH patients with differing disease severity and impact.

Results: em PH asis-10 scores discriminated subgroups of patients stratified on FC (ANOVA F=1.73; p<0.001); mean difference between FC II and FC III was 11.7 and between FC III and FC IV was 7.6. Participants who were in fulltime work had significantly lower em PH asis-10 scores (n=25, mean=19.6±12) compared to those not in any work (n=154, mean=30±10) (p<0.001). em PH asis-10 scores where significantly higher in patients receiving oxygen therapy (n=86, mean 31) compared to those not receiving oxygen (n=129, mean=25) (p=0.001). em PH asis-10 correlations were moderate for 6MWD (r = -041) and strong for psychological distress (HAD r = 0.77) and breathlessness (r = 0.74).

Conclusions: The em PH asis-10 is sensitive to differences in clinical parameters. It is strongly associated with measures of PH impact and should provide a useful tool for patient assessment in busy PH clinics.
COPD patients with more severe GOLD stages have higher serum cystatin C levels
Authors: Adam Nowinski, Damian Korzybski, Dariusz Kaminski, Anna Stoklosa, Dorota Gorecka
Journal: European Respiratory Journal (2012)

INTRODUCTION: Creatinine is widely used as a biomarker of kidney function but may be inaccurate at detecting mild renal impairment since creatinine levels may vary with muscle mass and protein intake. Advanced COPD is characterized by wasting of skeletal muscles and imbalances in protein metabolism.  Cystatin C may be used as a muscle independent biomarker of kidney function. Recently, it has been studied as a predictor of cardiovascular diseases and emphysema development.  AIM: The aim of this study was to evaluate the relationships between COPD severity and serum cystatin C levels in prospective study.  MATERIALS AND METHODS: One center longitudinal prospective study in COPD patients was designed. Consecutive COPD patients treated in respiratory department and healthy health care workers were studied. Serum levels of cystatin C, creatinine and urea were measured and glomerular filtration rate (GFR) was assessed.  RESULTS: 98 COPD patients and 29 non-COPD healthy controls were analyzed. GOLD stages and biochemistry parameters are shown in the table (* p  CONCLUSIONS: COPD patients with more severe GOLD stages have higher serum cystatin C levels but not creatinine or calculated creatinine clearence levels.
Abstract 2208: Chronic Performances of a New Lumenless Compared With Stylet-Delivered Pacing Leads in the Young With Congenital Heart
Authors: Asra Khan, Kathleen Zelin, Peter P Karpawich
Journal: Circulation (2009)

Background: United States’ approval of the model 3830 lead (Medtronic, Inc) in patients (pt) with congenital heart disease (CHD) was in 2005. The 4.1mm diameter, lumenless lead uses a flexible deli...
Use of Recombinant Human Granulocyte Colony-Stimulating Factor to Increase Chemotherapy Dose-Intensity: A Randomized Trial in Very High-Risk Childhood Acute Lymphoblastic Leukemia
Authors: G. Michel, J. Landman-Parker, M.F. Auclerc, C. Mathey, T. Leblanc, E. Legall, P. Bordigoni, J.P. Lamagnere, F. Demeocq, Y. Perel, A. Auvrignon, C. Berthou, F. Bauduer, B. Pautard, P. Schneider, G. Schaison, G. Leverger, A. Baruchel
Journal: Journal of Clinical Oncology (2000)

To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
Breast Cancer Risk Assessment: A Guide for Clinicians Using the NCCN Breast Cancer Risk Reduction Guidelines
Authors: Sofia D. Merajver, Kara Milliron
Journal: Journal of the National Comprehensive Cancer Network (2003)

Breast cancer, a complex and heterogeneous disease, is the most common malignancy diagnosed in women in the United States, with over 180,000 new cases and approximately 44,000 deaths per year. Breast cancer risk is influenced by a large number of factors, including age, family history, reproductive and hormonal history, proliferative breast conditions, physical activity, diet, and environmental exposures. These factors all interact in a complex manner to contribute to the risk of developing breast cancer. Because the interactions between risk factors are poorly understood at the molecular level, it is difficult to accurately evaluate the breast cancer risk of a given person presenting with an individual constellation of factors. To better define the population at increased risk that may warrant specific intervention, several models exist to estimate a woman's risk for developing breast cancer and for harboring a germline mutation in a cancer susceptibility gene. This article summarizes these models and gives brief guidelines about which model may be preferable given a specific family history.
Predicting the risk of bacteremia in childen with fever and neutropenia.
Authors: W R Rackoff, R Gonin, C Robinson, S G Kreissman, P B Breitfeld
Journal: Journal of Clinical Oncology (1996)

PURPOSE We sought to identify factors assessable at the time of admission for fever and neutropenia that predict bacteremia in children with cancer. PATIENTS AND METHODS One hundred fifteen consecutive episodes of fever and absolute neutrophil count (ANC) less than 500/microliter in 72 children with cancer were studied prospectively to determine the risk of bacteremia using data assessable at the time of presentation. After exploratory analysis identified admission temperature and absolute monocyte count (AMoC) as the strongest predictive factors, recursive partitioning was used to determine cutpoints for these variables that resulted in discrimination between episodes associated with a lower or higher risk of bacteremia. RESULTS There were 24 episodes of bacteremia (21% of episodes). Episodes were grouped using the cutpoints for AMoC and temperature: 17% were classified as low risk for bacteremia (AMoC &gt; or = 100/microliter), 65% as intermediate risk (AMoC &lt; 100/microliter and temperature &lt; 39.0 degrees C), and 18% as high risk (AMoC &lt; 100/microliter and temperature &gt; or = 39.0 degrees C). No episodes classified as low risk were associated with bacteremia; 19% of intermediate-risk and 48% of high-risk episodes were associated with bacteremia. The odds ratio of bacteremia for the high-risk versus the intermediate-risk group is 4.4 (95% confidence interval, 1.6 to 12.9). The risk classification was validated using data from 57 different episodes of fever and neutropenia treated in the same hospital. CONCLUSION Three levels of risk for bacteremia are defined using the AMoC and temperature at the time of admission for fever and neutropenia. Trials now should be conducted to test whether these factors may be used to assign some children to less intensive or outpatient antibiotic therapy at the time of presentation with fever and neutropenia.
Fortnightly review: seasonal allergic rhinitis
Authors: A. Parikh, G. K Scadding
Journal: BMJ (1997)

Seasonal allergic rhinitis or hay fever was called "catarrhus aestivus" (spring catarrh) in 19th century medical literature, but more recently has been labelled as a "post industrial revolution epidemic." 1 Its prevalence has increased in developed countries, particularly in the past two decades. 2One in six people is affected by allergic rhinitis. 3In 1990 the estimated cost of hay fever in the United States was $1.8 billion. 4ffective medication for this condition is available, and prophylactic treatment (topical corticosteroids, sodium cromoglycate) should be started two to three weeks before the pollen season to prevent priming by allergen.This year the warm spring has advanced the pollen season by two to three weeks and treatment should be started earlier.After concern over the risk of cardiac arrhythmias, the Medicines Control Agency is currently converting terfenadine, a commonly used antihistamine that is available over the counter, into a prescription only drug. Methodsost of the articles selected were from the personal library of GKS, who has 10 years of clinical and research experience in this subject.For an overview, we selected book chapters that had been written by leaders in the subject, while we selected individual papers for details of particular aspects of seasonal allergic rhinitis.Drug related details came from the British National Formulary, manufacturers' product data, and documents from the Medicines Control Agency. AllergensSeasonal allergic rhinitis is a type I immediate hypersensitivity reaction mediated by specific IgE antibody to a seasonal allergen, leading to mucosal inflammation characterised by sneezing, itching, rhinorrhoea, and nasal blockage.Pollens from wind pollinated grasses, trees, weeds, and spores from fungi are the commonest aeroallergens.Pollens are the male gametes of plants, and most antigenic pollens are 6-40 m in diameter.Larger pollens from oil seed rape, which is pollinated by insects, have recently been implicated as causative agents. 5Timing Grass pollen is the commonest cause of seasonal allergic rhinitis in Britain. 6The highest levels of pollen in
Abstract 184: Exposure To Air Pollution In Utero Causes Persistent Cardiovascular Dysfunction
Authors: Loren Wold, Matthew Gorr, Clayton Eichenseer, Dane Youtz, Markus Velten
Journal: Circulation Research (2014)

Exposure to air pollutants during pregnancy can have devastating effects on offspring, inducing intrauterine growth retardation and maturation deficits. These developmental insufficiencies can affect the formation and function of the adult heart. We hypothesized that exposure to air pollution in utero would induce abnormal cardiac function at adulthood. FVB mice were exposed (6h/day, 7d/wk) to environmentally relevant concentrations of ambient particulate matter (PM2.5) or filtered air (FA) beginning when animals were paired for breeding. After birth, both groups remained in FA. Cardiac echocardiography was performed at 10 weeks of age. Birth weight was reduced in pups exposed to PM2.5 during intrauterine development compared to FA exposed pups, and litter size did not differ significantly between groups. Echocardiography revealed reduced left ventricular fractional shortening with greater left ventricular end systolic diameter in PM2.5 exposed mice at 10 weeks of age. These results were similar to data from mice exposed perinatally (until weaning). This study supports the hypothesis that exposure to air pollution in utero can lead to heart dysfunction at adulthood.
Unsupervised surgical training
Authors: C. Galasko, C. MacKay, R. G Notley, D. C O'Riordan, N. Shaper
Journal: BMJ (1997)

More widespread public debate on rationing is essentialEditor-We find it significant that none of the clinicians who contributed to the conference "Rationing in the NHS: Time to Get Real" signed the open letter to Frank Dobson. 1 In the letter, rationing is defined as occurring when not all health services can be provided to everybody who might benefit from them, a definition so broad that it can be said always to have existed.Yet most British clinicians would not recognise the examples given as rationing.A young woman with high cholesterol as a single risk factor for coronary heart disease may be "denied" drug treatment and given dietary advice instead simply because the risks of side effects outweigh the marginal benefit; this is rational, not rationing.Again, "denying" magnetic resonance imaging for uncomplicated migraine in a young person has nothing to do with cost: the risks of iatrogenic anxiety and distress are far greater than any possible benefit from such intervention.The authors do the cause of so called smart rationing a disservice by these examples.This debate is too important to be "dumbed down" in this way.Whenever rationing is discussed there is a tension between those whose professional discipline (health economics, medical ethics, or policy analysis) allows them to work with broad underlying principles and those who are constantly brought face to face with the limitations of these principles through daily contact with patients.The former are much more likely to believe that it is possible and appropriate to base all rationing decisions on a series of well argued principles.Life for the latter is far messier: it is often impossible to apply broad principle to individual cases, let alone find a "currency of comparison" 2 that will enable the claims of, for example, a dying older person on an understaffed geriatric ward to be ranked against those of a patient with multiple sclerosis who might benefit from interferon beta.Struggling to make these sorts of comparisons is painful; the examples given in the open letter tax no one and thereby offer false hope of easy solutions.It is because the choices are difficult that more widespread public debate is essential.Only through such a debate can we all, as citizens, realise what is happening to the NHS, consider if that is the NHS that we want, and decide how much of our taxes an NHS worthy of the name deserves.