tbuckley/cabot-search huggingface dataset:
Objective assessment of technical skills in surgery
Authors: James P B O'Connor
Journal: BMJ (2004)

Editor—Moorthy et al highlight the need to assess surgical trainees' skills reliably and accurately, outlining options available to achieve this end.1 Inadequate objective skill based assessment and poor knowledge of basic science are major concerns for both trainers and trainees alike.

However, the context in which skills and facts are acquired is just as important as method of assessment. Basic and higher surgical training are currently clinically based, supplemented by courses, educational meetings, and tutorials.

Unfortunately, many trainees attend the course for basic surgical skills well into their training. Some partially fund such courses because of limited deanery budgets or are denied study leave because of service commitments. Training schemes seldom offer revision of anatomy or physiology in the dissection room or laboratory from basic science staff.

In contrast, trainee chartered accountants enjoy the benefit of several structured, month long, free courses between work placements. Pass rates exceed comparable surgical examinations, and trainees receive useful career preparation.

The surgical royal colleges acknowledge that training needs restructuring.2 I suggest that protected, structured blocks of teaching and assessing basic sciences and skills should be provided throughout surgical training. Proposed changes to training present an ideal opportunity to implement such modules.3

Objections are predictable. It would be costly. Trainees would require release from some service commitments. Postgraduate training would have to be properly organised. Difficulties arise in the objective assessment of trainees.4 But if surgical teaching and assessment is to improve then the solution must be more radical than formulating another three day course, or adding an extra examination.
Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis
Authors: R. William Vandivier, Valerie A. Fadok, Peter R. Hoffmann, Donna L. Bratton, Churee Penvari, Kevin K. Brown, Joseph D. Brain, Frank J. Accurso, Peter M. Henson
Journal: Journal of Clinical Investigation (2002)

Cystic fibrosis is characterized by an early and sustained influx of inflammatory cells into the airways and by release of proteases. Resolution of inflammation is normally associated with the orderly removal of dying apoptotic inflammatory cells through cell recognition receptors, such as the phosphatidylserine receptor, CD36, and alpha v integrins. Accordingly, removal of apoptotic inflammatory cells may be impaired in persistent inflammatory responses such as that seen in cystic fibrosis airways. Examination of sputa from cystic fibrosis and non-cystic fibrosis bronchiectasis patients demonstrated an abundance of apoptotic cells, in excess of that seen in patients with chronic bronchitis. In vitro, cystic fibrosis and bronchiectasis airway fluid directly inhibited apoptotic cell removal by alveolar macrophages in a neutrophil elastase-dependent manner, suggesting that elastase may impair apoptotic cell clearance in vivo. Flow cytometry demonstrated that neutrophil elastase cleaved the phosphatidylserine receptor, but not CD36 or CD32 (Fc gamma RII). Cleavage of the phosphatidylserine receptor by neutrophil elastase specifically disrupted phagocytosis of apoptotic cells, implying a potential mechanism for delayed apoptotic cell clearance in vivo. Therefore, defective airway clearance of apoptotic cells in cystic fibrosis and bronchiectasis may be due to elastase-mediated cleavage of phosphatidylserine receptor on phagocytes and may contribute to ongoing airway inflammation.
Randomised controlled trial of azithromycin in smokers with asthma: Table 1–
Authors: Euan J. Cameron, Rekha Chaudhuri, Frances Mair, Charles McSharry, Nicola Greenlaw, Christopher J. Weir, Lisa Jolly, Iona Donnelly, Katie Gallacher, Deborah Morrison, Mark Spears, Tom J. Evans, Kenneth Anderson, Neil C. Thomson
Journal: European Respiratory Journal (2013)

To the Editor: 

Smokers with asthma have poor symptom control, accelerated decline in lung function and an attenuated response to corticosteroids compared to nonsmokers with asthma [1]. There is an unmet need for alternative or additional drugs for smokers with asthma who are unable to stop smoking [2]. Macrolide antibiotics have anti-inflammatory activity [3] and in clinical studies there is good evidence for efficacy in the treatment of diffuse pan-bronchiolitis and cystic fibrosis, as well as in preventing chronic rejection after lung transplantation [4, 5]. In asthma, chronic treatment is associated with a reduction in bronchial hyperreactivity in mild-to-moderate asthma [6] and in exacerbation rates in non-eosinophilic severe asthma [7]. To date, no studies have examined the efficacy of macrolide antibiotics exclusively in current smokers with asthma.

A randomised double-blind parallel-group trial compared azithromycin, 250 mg per day, with placebo for 12 weeks. All subjects were aged 18–70 years, were current smokers (≥5 pack-years history) with chronic asthma (>1 year duration; defined by international criteria [8]) and had to be free of exacerbation and respiratory tract infection for a minimum 6-week period prior to randomisation. A baseline visit was performed following a 4-week run-in period on inhaled corticosteroid (ICS) therapy equivalent to 400 μg beclometasone ± a long-acting β2-agonist (LABA). Ethical approval was obtained and all subjects provided written informed consent. Study visits were performed at 4, 8 and 12 weeks. Clinic visit peak expiratory flow (PEF) after 12 weeks treatment was the primary outcome measure. A sample size of 68 …
Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease
Authors: H Taniguchi, S Katoh, J Kadota, Y Matsubara, K Fukushima, H Mukae, S Matsukura, S Kohno
Journal: European Respiratory Journal (2000)

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.
Effect of Guanethidine and Bretylium on the Dog Heart-Lung Preparation
Authors: TOM E. GAFFNEY
Journal: Circulation Research (1961)

Inotropic and chronotropic effects of guanethidine and bretylium have been observed in heart-lung preparations made from normal and chronically reserpinized dogs. Guanethidine (0.3 to 30 mg.) in the untreated preparation had marked positive inotropic and chronotropic effects, whereas after pretreatment with reserpine it had a striking negative inotropic effect and no effect on heart rate. Guanethidine given to preparations made from animals pretreated with guanethidine had a negative inotropic effect smaller than that seen after reserpine pretreatment. Bretylium (0.3 to 30 mg.) in the untreated preparation had both positive inotropic and positive chronotropic effects. In the chronically reserpinized animal, the positive inotropic effect of bretylium persisted though it was reduced to about one-quarter of the original size. The positive chronotropic effect of bretylium in this circumstance was reversed to a negative chronotropic effect. These effects are interpreted as indirect but strong evidence that: (1) guanethidine and bretylium exert at least part of their initial positive inotropic and chronotropic effects by a release of catecholamines; and (2) in the amine-depleted heart, guanethidine has an intrinsic negative inotropic effect, whereas bretylium has an intrinsic positive inotropic effect.
Targeting CD20 in Melanoma Patients at High Risk of Disease Recurrence
Authors: Alice Pinc, Rajasekharan Somasundaram, Christine Wagner, Marcus Hörmann, Georgios Karanikas, Ahmad Jalili, Wolfgang Bauer, Patrick Brunner, Katharina Grabmeier-Pfistershammer, Melanie Gschaider, Chiou-Yan Lai, Mei-Yu Hsu, Meenhard Herlyn, Georg Stingl, Stephan N Wagner
Journal: Molecular Therapy (2012)

Melanomas contain distinct cell subpopulations. Several of these subpopulations, including one expressing CD20, may harbor stem cell-like or tumor-initiating characteristics. We hypothesized that patients at high risk of disease recurrence could benefit from an adjuvant anti-CD20 therapy. Therefore, we initiated a small pilot trial to study the effect of the anti-CD20 antibody rituximab in a group of melanoma patients with stage IV metastatic disease who had been rendered without evident disease by way of surgery, chemotherapy and/or radiation therapy. The major objective was safety, while secondary objectives were description of recurrence-free intervals (RFI) and overall survival (OS). Nine patients received rituximab at 375 mg/m2 qw for 4 weeks followed by a maintenance therapy every 8 weeks. Treatment was discontinued after 2 years or with disease recurrence. Treatment was well tolerated. After a median observation of 42 months, the median neither of RFI nor of OS has been reached. Despite therapy that ended after 2 years, six out of nine patients are still alive and five of them are recurrence-free. Though the patient number is too small for definitive conclusions, our data may represent a first example of the potential therapeutic value of targeting CD20+ cell populations—at least for a subset of patients. Melanomas contain distinct cell subpopulations. Several of these subpopulations, including one expressing CD20, may harbor stem cell-like or tumor-initiating characteristics. We hypothesized that patients at high risk of disease recurrence could benefit from an adjuvant anti-CD20 therapy. Therefore, we initiated a small pilot trial to study the effect of the anti-CD20 antibody rituximab in a group of melanoma patients with stage IV metastatic disease who had been rendered without evident disease by way of surgery, chemotherapy and/or radiation therapy. The major objective was safety, while secondary objectives were description of recurrence-free intervals (RFI) and overall survival (OS). Nine patients received rituximab at 375 mg/m2 qw for 4 weeks followed by a maintenance therapy every 8 weeks. Treatment was discontinued after 2 years or with disease recurrence. Treatment was well tolerated. After a median observation of 42 months, the median neither of RFI nor of OS has been reached. Despite therapy that ended after 2 years, six out of nine patients are still alive and five of them are recurrence-free. Though the patient number is too small for definitive conclusions, our data may represent a first example of the potential therapeutic value of targeting CD20+ cell populations—at least for a subset of patients.
Evaluation of LMP1 of Epstein-Barr virus as a therapeutic target by its inhibition
Authors: Adele Hannigan, Joanna B Wilson
Journal: Molecular Cancer (2010)

The latent membrane protein-1 (LMP1) encoded by Epstein-Barr virus (EBV) is an oncoprotein which acts by constitutive activation of various signalling pathways, including NF-kappaB. In so doing it leads to deregulated cell growth intrinsic to the cancer cell as well as having extrinsic affects upon the tumour microenvironment. These properties and that it is a foreign antigen, lead to the proposition that LMP1 may be a good therapeutic target in the treatment of EBV associated disease. LMP1 is expressed in several EBV-associated malignancies, notably in Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC). However, the viral protein is only detected in approximately 30%-50% of NPC samples, as such its role in carcinogenesis and tumour maintenance can be questioned and thus its relevance as a therapeutic target.In order to explore if LMP1 has a continuous function in established tumours, its activity was inhibited through expression of a dominant negative LMP1 mutant in tumour cell lines derived from transgenic mice. LMP1 is the tumour predisposing oncogene in two different series of transgenic mice which separately give rise to either B-cell lymphomas or carcinomas. Inhibition of LMP1 activity in the carcinoma cell lines lead to a reduction in clonagenicity and clone viability in all of the cell lines tested, even those with low or below detection levels of LMP1. Inhibition of LMP1 activity in the transgenic B-cell lines was incompatible with growth and survival of the cells and no clones expressing the dominant negative LMP1 mutant could be established.LMP1 continues to provide a tumour cell growth function in cell lines established from LMP1 transgenic mouse tumours, of both B-cell and epithelial cell origin. LMP1 can perform this function, even when expressed at such low levels as to be undetectable, whereby evidence of its expression can only be inferred by its inhibition being detrimental to the growth of the cell. This raises the possibility that LMP1 still performs a pro-oncogenic function in the 50% to 70% of NPC tumours wherein LMP1 protein expression cannot be detected. This reinforces the basis for pursuing LMP1 as a therapeutic target in EBV associated LMP1-expressing malignancies.
Functional analysis of splice site mutations in the human hairless (<i>HR</i>) gene using a minigene assay
Authors: M. Refke, S.M. Pasternack, B. Fiebig, S. Wenzel, N. Ishorst, M. Ludwig, M.M. Nöthen, M.M. Seyger, B.C. Hamel, R.C. Betz
Journal: British Journal of Dermatology (2011)

Congenital atrichia is a rare autosomal recessive form of isolated alopecia which is caused by mutations in the human hairless (HR) gene. Patients are born with normal hair that is shed almost completely and irreversibly during the first weeks of life.To investigate the molecular genetic basis of congenital atrichia in two patients, and to analyse the functional consequences of one newly identified and all seven previously identified HR splice site mutations using a minigene assay.Molecular analysis of the HR gene was performed by direct DNA sequencing. To analyse the functional consequences of the splice site mutations, the respective sequences were cloned into a vector which allows directed splicing. After transfection of COS7 cells, isolation of RNA and cDNA synthesis, sequencing was performed to analyse the products.Two novel mutations were identified: an insertion in exon 2 (c.485insT; p.C162LfsX17), and a splice site mutation (c.2847-1G>A). In vitro analysis revealed aberrant splicing for all eight of the investigated HR splice site mutations. Comparison with the results of two biocomputational programs (neural network splice server and CRYP-SKIP) and calculation of consensus values revealed that the predictions of these two programs were consistent in only five and two of the eight mutations, respectively.This is the first report to analyse the consequences of HR splice site mutations using a cell-based in vitro assay. The results highlight the importance of performing splicing experiments to clarify the consequences of putative splice site mutations.
Site of Action of Hypertonic Saline in the Pulmonary Circulation
Authors: M. ELIAKIM, S. STERN, H. NATHAN
Journal: Circulation Research (1961)

The effect of intravenous injections of 20 per cent saline on the pulmonary circulation was examined in 19 dogs. A marked rise of pulmonary arterial pressure was recorded in all cases. The pressure changes in the pulmonary veins depended largely on the choice of the vein for pressure measurements. A hypertensive response was usually recorded in the superior vein, while in the inferior vein no change or a slight fall in pressure was the rule. Left atrial pressure either did not change or fell. A difference in the anatomical structure of the muscle sphincter around the superior and inferior pulmonary veins is described. A potent sphincter surrounds the superior veins and infiltrates within their walls some-times as far as the border of the lung. The sphincter around the inferior veins is rudimentary and inconspicuous. Evidence is brought that hypertonic saline acts both on the pulmonary veins close to the left atrium and at the pulmonary arteriolar level.
Permanent Genetic Tagging of Podocytes
Authors: Takako Asano, Fumio Niimura, Ira Pastan, Agnes B. Fogo, Iekuni Ichikawa, Taiji Matsusaka
Journal: Journal of the American Society of Nephrology (2005)

Injured podocytes lose differentiation markers. Therefore, the true identity of severely injured podocytes remains unverified. A transgenic mouse model equipped with a podocyte-selective injury induction system was established. After induction of podocyte injury, mice rapidly developed glomerulosclerosis, with downregulation of podocyte marker proteins. Proliferating epithelial cells accumulated within Bowman's space, as seen in collapsing glomerulosclerosis. In this study, the fate of injured podocytes was pursued. Utilizing Cre-loxP recombination, the podocyte lineage was genetically labeled with lacZ in an irreversible manner. After podocyte injury, the number of lacZ-labeled cells, which were often negative for synaptopodin, progressively declined, correlating with glomerular damage. Parietal epithelial cells, but not lacZ-labeled podocytes, avidly proliferated. The cells proliferating within Bowman's capsule and, occasionally, on the outer surface of the glomerular basement membrane were lacZ-negative. Thus, when podocytes are severely injured, proliferating parietal epithelial cells migrate onto the visceral site, thereby mimicking proliferating podocytes.
Vasculin, a novel vascular protein differentially expressed in human atherogenesis
Authors: Ann P. J. J. Bijnens, Ann Gils, Barry Jutten, Birgit C. G. Faber, Sylvia Heeneman, Peter J. E. H. M. Kitslaar, Jan H. M. Tordoir, Carlie J. M. de Vries, Abraham A. Kroon, Mat J. A. P. Daemen, Kitty B. J. M. Cleutjens
Journal: Blood (2003)

Recent suppressive subtractive hybridization analysis on human atherosclerotic plaque-derived RNA revealed genes upregulated in plaques with a thrombus versus stable plaques. Clone SSH6, containing part of a putative open reading frame of an unknown protein, was further investigated. Full-length cDNA, coding for a 473-amino acid (aa) protein, was identified in a vascular smooth muscle cell (SMC) cDNA library. Bioinformatics suggested the presence of multiple SSH6 variants due to alternative splicing of exon 3. Multiple-tissue Northern blot analysis demonstrated a differential expression pattern of these variants, as a ubiquitously expressed SSH6 mRNA missing exon 3, was detected apart from a putative vascular SMC-specific form containing exon 3. Western blot analysis indicated a ubiquitous 35-kDa protein (SSH6-beta), in addition to a 45-kDa protein (vasculin), detected in the vascular wall and in plasma. Analysis of arteries displaying various stages of atherosclerosis indicated that the vasculin/SSH6-beta ratio increases throughout atherogenesis. Immunohistochemical analysis demonstrated cytoplasmic expression of SSH6 gene products in macrophages, endothelial cells, and SMCs. In summary, we identified a novel mRNA/protein, vasculin, in the arterial wall and plasma. The regulated expression of vasculin in plaques suggests a role in atherogenesis. Moreover, its presence in plasma opens perspectives for vasculin as a marker for atherosclerosis.
Genomic and small RNA sequencing of Miscanthus × giganteus shows the utility of sorghum as a reference genome sequence for Andropogoneae grasses
Authors: Kankshita Swaminathan, Magdy S Alabady, Kranthi Varala, Emanuele De Paoli, Isaac Ho, Dan S Rokhsar, Aru K Arumuganathan, Ray Ming, Pamela J Green, Blake C Meyers, Stephen P Moose, Matthew E Hudson
Journal: Genome biology (2010)

Abstract Background Miscanthus × giganteus ( Mxg ) is a perennial grass that produces superior biomass yields in temperate environments. The essentially uncharacterized triploid genome (3n = 57, x = 19) of Mxg is likely critical for the rapid growth of this vegetatively propagated interspecific hybrid. Results A survey of the complex Mxg genome was conducted using 454 pyrosequencing of genomic DNA and Illumina sequencing-by-synthesis of small RNA. We found that the coding fraction of the Mxg genome has a high level of sequence identity to that of other grasses. Highly repetitive sequences representing the great majority of the Mxg genome were predicted using non-cognate assembly for de novo repeat detection. Twelve abundant families of repeat were observed, with those related to either transposons or centromeric repeats likely to comprise over 95% of the genome. Comparisons of abundant repeat sequences to a small RNA survey of three Mxg organs (leaf, rhizome, inflorescence) revealed that the majority of observed 24-nucleotide small RNAs are derived from these repetitive sequences. We show that high-copy-number repeats match more of the small RNA, even when the amount of the repeat sequence in the genome is accounted for. Conclusions We show that major repeats are present within the triploid Mxg genome and are actively producing small RNAs. We also confirm the hypothesized origins of Mxg , and suggest that while the repeat content of Mxg differs from sorghum, the sorghum genome is likely to be of utility in the assembly of a gene-space sequence of Mxg .
Serum IgE Concentrations in Bullous Pemphigoid Correlate with Disease Activity
Authors: L.A. Kelly, R. Holubkov, M.A. Campbell, K.S. Herlevi, T. Taylor, C. Hull, G.J. Gleich, J.J. Zone, K.M. Leiferman
Journal: Journal of Allergy and Clinical Immunology (2007)
Authors' Response to Hogan
Authors: Bart L Haagmans, Albert D. M. E Osterhaus
Journal: PLoS Medicine (2006)

Because of the nature of the analysis used in this study [1], no conclusion is possible.There are plenty of examples in the literature demonstrating the "ecological fallacy".Studies such as this have very little utility other than to generate hypotheses.I tend to think that this association is a marker for greater recognition and treatment for depression.However, it's a brave epidemiologist who would draw any conclusions at all from an ecological association such as this where the outcome is relatively rare.
Atrial Fibrillation and Heart Failure in Cardiology Practice: Reciprocal Impact and Combined Management From the Perspective of Atrial Fibrillation
Authors: Robby Nieuwlaat, Luc W. Eurlings, John G. Cleland, Stuart M. Cobbe, Panos E. Vardas, Alessandro Capucci, José L. López-Sendòn, Joan G. Meeder, Yigal M. Pinto, Harry J.G.M. Crijns
Journal: Journal of the American College of Cardiology (2009)