tbuckley/cabot-search huggingface dataset:
ABC of learning and teaching in medicine: Problem based learning
Authors: D. F Wood
Journal: BMJ (2003)

Problem based learning is used in many medical schools in the United Kingdom and worldwide. This article describes this method of learning and teaching in small groups and explains why it has had an important impact on medical education.

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The group learning process: acquiring desirable learning skills

In problem based learning (PBL) students use “triggers” from the problem case or scenario to define their own learning objectives. Subsequently they do independent, self directed study before returning to the group to discuss and refine their acquired knowledge. Thus, PBL is not about problem solving per se, but rather it uses appropriate problems to increase knowledge and understanding. The process is clearly defined, and the several variations that exist all follow a similar series of steps.

#### Generic skills and attitudes

Group learning facilitates not only the acquisition of knowledge but also several other desirable attributes, such as communication skills, teamwork, problem solving, independent responsibility for learning, sharing information, and respect for others. PBL can therefore be thought of as a small group teaching method that combines the acquisition of knowledge with the development of generic skills and attitudes. Presentation of clinical material as the stimulus for learning enables students to understand the relevance of underlying scientific knowledge and principles in clinical practice.

However, when PBL is introduced into a curriculum, several other issues for curriculum design and implementation need to be tackled. PBL is generally introduced in the context of a defined core curriculum and integration of basic and clinical sciences. It has implications for staffing and learning resources and demands a different approach to timetabling, workload, and assessment. PBL is often used to deliver core material in non-clinical parts of the …

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Interleukin 13 Is Secreted by and Stimulates the Growth of Hodgkin and Reed-Sternberg Cells
Authors: Ursula Kapp, Wen-Chen Yeh, Bruce Patterson, Andrew J. Elia, David Kägi, Alexandra Ho, Andrew Hessel, Mike Tipsword, Alexia Williams, Christine Mirtsos, Annick Itie, Matthew Moyle, Tak W. Mak
Journal: The Journal of Experimental Medicine (1999)

Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.
A new cardiac prosthesis: the St. Jude Medical cardiac valve: in vivo results.
Authors: R W Emery, E Mettler, D M Nicoloff
Journal: Circulation (1979)

The St. Jude Medical cardiac valve prosthesis is a low profile, lightweight, bi-leaflet, central-flow device constructed entirely of pyrolytic carbon. In vivo testing was performed in 24 cows in which the tricuspid valve (n = 14) or mitral valve (n = 10) was replaced by a St. Jude Medical prosthesis with a 26 mm tissue annulus diameter. Eight animals died in the operative period. The 16 surviving animals were sacrificed at 4, 8, 12, or 18 weeks. There were no valve-related deaths nor mechanical valve failures. Anticoagulation was not used in the postoperative period during which time monthly laboratory parameters were obtained including hemoglobin, hematocrit, white cell count, red cell count and indices, lactic acid dehydrogenase, serum haptoglobin, and, additionally at sacrifice, platelet and red cell morphology. Values indicated this prosthesis did not cause hemolysis. At sacrifice the pulmonary arterial tree and peripheral organs showed no evidence of thromboemboli. There was smooth endocardial ingrowth on all valve sewing rings. One valve had thrombus formation on the valve sewing ring. Nine animals were anesthetized prior to sacrifice and underwent open cardiac catheterization. Ventriculography (n = 6) showed minimal transvalvar reflux, and atriograms (n = 6) demonstrated central flow. Transvalvar gradients were 0 to 22 mm Hg (n = 9). One valve of an 18-week tricuspid implant was examined for wear; valve life was calculated to be greater than 2500 years. These data in conjunction with in vitro test results justify clinical trial of the St. Jude Medical prosthesis.
Up-regulation of the multidrug resistance genes,<i>Mrp1</i>and<i>Mdr1b</i>, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver
Authors: Thera A. Vos, Guido J. Hooiveld, Hans Koning, Sarah Childs, Dirk K. Meijer, Han Moshage, Peter L. Jansen, Michael Müller
Journal: Hepatology (1998)

Endotoxin–induced cholestasis is mainly caused by an impaired canalicular secretion. Mrp2, the canalicular multispecific organic anion transporter, is strongly down–regulated in this situation, and canalicular bile salt secretion is also reduced. We hypothesized that other adenosine triphosphate-binding cassette (ABC) transporters may compensate for the decreased transport activity to protect the cell from cytokine–induced oxidative damage. Therefore, we examined the expression of ABC–transport proteins in membrane fractions of whole liver and of isolated hepatocytes of endotoxin–treated rats and performed reverse–transcriptase polymerase chain reaction (RT–PCR) on mRNA isolated from these livers. In addition, the localization of these transporters was examined using confocal scanning laser microscopy. By 6 hours after endotoxin administration, we found a clear increase of mrp1 mRNA and protein, whereas mrp2 mRNA and protein were decreased. This was confirmed in isolated hepatocytes. In addition, mdr1b mRNA was strongly increased, whereas mdr1a and mdr2 mRNA did not change significantly. Both the mRNA and protein levels of the sister of P–glycoprotein (spgp), the recently cloned bile salt transporter, decreased. After endotoxin treatment, the normally sharply delineated canalicular staining of mrp2 and spgp had changed to a fuzzy pattern, suggesting localization in a subapical compartment. We conclude that endotoxin–induced cholestasis is caused by decreased mrp2 and spgp levels, as well as an abnormal localization of these proteins. The simultaneous up–regulation of mrp1 and mdr1b may confer resistance to hepatocytes against cytokine–induced metabolic stress.
Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children
Authors: T Islam, K Berhane, R McConnell, W J Gauderman, E Avol, J M Peters, F D Gilliland
Journal: Thorax (2008)

<h3>Background:</h3> Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (<i>GST</i>)<i>P1</i>, <i>GSTM1</i>, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. <h3>Methods:</h3> Associations of the well characterised null variant of <i>GSTM1</i> and four single nucleotide polymorphisms (SNPs) that characterised common variation in the <i>GSTP1</i> locus with new onset asthma in a cohort of 1610 school children were examined. Children’s exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. <h3>Results:</h3> A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between <i>GSTP1</i> and asthma. The risk of asthma was lower for those with the <i>Val</i> allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among <i>ile<sup>105</sup></i> homozygotes but not among those with at least one <i>val<sup>105</sup></i> allele (interaction p value = 0.02). The risk was highest among <i>ile<sup>105</sup></i> homozygotes who participated in ⩾3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). <i><i>GSTM1</i></i> null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. <h3>Conclusion:</h3> Children who inherit a <i>val<sup>105</sup></i> variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. <i><i>GSTM1</i></i> null genotype was associated with an increased risk of asthma.
Catecholamine-Induced Vascular Wall Growth Is Dependent on Generation of Reactive Oxygen Species
Authors: Tina Bleeke, Hua Zhang, Nageswara Madamanchi, Cam Patterson, James E. Faber
Journal: Circulation Research (2003)

α 1 -Adrenoceptor–dependent proliferation of vascular smooth muscle cells (VSMCs) is strongly augmented by vascular injury, and may contribute to intimal growth and lumen loss. Because reactive oxygen species (ROS) are increased by injury and have been implicated as second messengers in proliferation of VSMCs, we investigated the role of ROS in catecholamine-induced VSMC growth. Rat aortae were isolated 4 days after balloon injury, maintained in organ culture under circumferential wall tension, and exposed to agents for 48 hours. The antioxidants N-acetylcysteine (NAC, 10 mmol/L) and Tiron (5 mmol/L) and the flavin-inhibitor diphenylene iodonium (DPI, 20 μmol/L) abolished norepinephrine-induced increases in protein synthesis and DNA content in media. In aortic sections, norepinephrine augmented ROS production (dihydroethidium confocal microscopy), which was dose-dependently inhibited by NAC, Tiron, and DPI. In cultured VSMCs, phenylephrine caused time- and dose-dependent ROS generation (aconitase activity), had similar efficacy to thrombin (1 U/mL), and was eliminated by the superoxide dismutase (SOD) mimetic Mn-(III)-tetrakis-(4-benzoic-acid)-porphyrin-chloride (200 μmol/L) and Tiron. Phenylephrine-induced ROS production and increases in DNA and protein content were blocked by prazosin (0.3 μmol/L) and abolished in p47 phox −/− cells. PEG-SOD (25 U/mL) had little effect, whereas PEG-catalase (50 U/mL) eliminated phenylephrine-induced proliferation in VSMCs. DPI (10 μmol/L) and apocynin (30 μmol/L) abolished phenylephrine-stimulated mitogenesis, whereas inhibitors of other intracellular ROS sources had not effect. Furthermore, PE increased p47 phox expression (RT-PCR). These data demonstrate that the trophic effect of catecholamines on vascular wall cells is dependent on a ROS-sensitive step that we hypothesize consists of activation of the NAD(P)H-dependent vascular oxidase.
Parity still isn't a generalisation problem
Authors: R. I. Damper
Journal: Behavioral and Brain Sciences (1998)

Clark &amp; Thornton take issue with my claim that parity is not a generalisation problem, and that nothing can be inferred about back-propagation in particular, or learning in general, from failures of parity generalisation. They advance arguments to support their contention that generalisation is a relevant issue. In this continuing commentary, I examine generalisation more closely in order to refute these arguments. Different learning algorithms will have different patterns of failure: back-propagation has no special status in this respect. This is not to deny that a particular algorithm might fortuitously happen to produce the “intended” function in an (oxymoronic) parity-generalisation task.
Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease
Authors: JA Barbera, J Roca, A Ferrer, MA Felez, O Diaz, N Roger, R Rodriguez-Roisin
Journal: European Respiratory Journal (1997)

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.
Adjustments for Center in Multicenter Studies: An Overview
Authors: A. Russell Localio, Jesse A. Berlin, Thomas R. Ten Have, Stephen E. Kimmel
Journal: Annals of Internal Medicine (2001)

Increasingly, investigators rely on multicenter or multigroup studies to demonstrate effectiveness and generalizability. Authors too often overlook the analytic challenges in these study designs: the correlation of outcomes and exposures among patients within centers, confounding of associations by center, and effect modification of treatment or exposure across center. Correlation or clustering, resulting from the similarity of outcomes among patients within a center, requires an adjustment to confidence intervals and P values, especially in observational studies and in randomized multicenter studies in which treatment is allocated by center rather than by individual patient. Multicenter designs also warrant testing and adjustment for the potential bias of confounding by center, and for the presence of effect modification or interaction by center. This paper uses examples from the recent biomedical literature to highlight the issues and analytic options.
Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia
Authors: Sung Ok Park, Mamta Wankhede, Young Jae Lee, Eun-Jung Choi, Naime Fliess, Se-Woon Choe, Seh-Hoon Oh, Glenn Walter, Mohan K. Raizada, Brian S. Sorg, S. Paul Oh
Journal: Journal of Clinical Investigation (2009)

Arteriovenous malformations (AVMs) are vascular anomalies where arteries and veins are directly connected through a complex, tangled web of abnormal arteries and veins instead of a normal capillary network. AVMs in the brain, lung, and visceral organs, including the liver and gastrointestinal tract, result in considerable morbidity and mortality. AVMs are the underlying cause of three major clinical symptoms of a genetic vascular dysplasia termed hereditary hemorrhagic telangiectasia (HHT), which is characterized by recurrent nosebleeds, mucocutaneous telangiectases, and visceral AVMs and caused by mutations in one of several genes, including activin receptor–like kinase 1 (ALK1). It remains unknown why and how selective blood vessels form AVMs, and there have been technical limitations to observing the initial stages of AVM formation. Here we present in vivo evidence that physiological or environmental factors such as wounds in addition to the genetic ablation are required for Alk1-deficient vessels to develop to AVMs in adult mice. Using the dorsal skinfold window chamber system, we have demonstrated for what we believe to be the first time the entire course of AVM formation in subdermal blood vessels by using intravital bright-field images, hyperspectral imaging, fluorescence recordings of direct arterial flow through the AV shunts, and vascular casting techniques. We believe our data provide novel insights into the pathogenetic mechanisms of HHT and potential therapeutic approaches.
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial
Authors: John R Teerlink, Gad Cotter, Beth A Davison, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Piotr Ponikowski, Elaine Unemori, Adriaan A Voors, Kirkwood F Adams, Maria I Dorobantu, Liliana R Grinfeld, Guillaume Jondeau, Alon Marmor, Josep Masip, Peter S Pang, Karl Werdan, Sam L Teichman, Angelo Trapani, Christopher A Bush, Rajnish Saini, Christoph Schumacher, Thomas M Severin, Marco Metra
Journal: The Lancet (2012)
Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells
Authors: Veronica Fernandez-Ruiz, Milosz Kawa, Carmen Berasain, Maria Iñiguez, Volker Schmitz, Eduardo Martinez-Ansó, Mercedes Iñarrairaegui, Ignacio Herrero, Bruno Sangro, Delia D´Avola, Jorge Quiroga, Cheng Qian, Jesus Prieto
Journal: Journal of Hepatology (2011)
Users' Guides to the Medical Literature
Authors: Andreas Laupacis
Journal: JAMA (1994)

<h3>CLINICAL SCENARIO</h3> You are about to see a 76-year-old retired schoolteacher for the second time. You first saw her in the clinic a month ago because of cognitive problems. Your evaluation at that time included a Standardized Mini-Mental State Examination,<sup>1</sup>on which she scored 18 out of a possible 30 points, and a physical examination that was normal including no focal neurological signs. You arranged investigations for the treatable causes of dementia that were negative, and you thus feel she has probable Alzheimer's disease. The patient has lived with her son since her husband died 6 years ago. Her son thinks that she first developed significant problems with her memory about 3 years ago. However, she has become increasingly agitated and paranoid during the last year. She has refused to allow him to look after her financial affairs, despite the fact that she owns three pieces of property and
Miniature Battery Foreign Bodies in Auditory and Nasal Cavities
Authors: Kevin T. Kavanagh
Journal: JAMA (1986)

A series of cases involving button batteries lodged in the ear or nasal cavity is presented. All produced tissue destruction. Injuries were generally severe, and included tympanic membrane perforation (three patients) or total destruction (three), marked necrosis of dermis of the external ear canal with exposed bone (seven), documented further impairment of hearing (three), destruction of ossicles (two), facial nerve paralysis and chondritis (one), nasal septal perforation (one), and superficial burns of nasal mucosa (one). Otic and nasal drops must be withheld as they provide an external electrolyte bath for the battery, enhancing leakage and generation of an external current, with subsequent tissue electrolysis and hydroxide formation. Instead, batteries lodged in the ear or nose must be removed promptly. (<i>JAMA</i>1986;255:1470-1472)
Medical Treatment of Advanced Testicular Cancer
Authors: Darren R Feldman, George J Bosl, Joel Sheinfeld, Robert J Motzer
Journal: JAMA (2008)

The medical treatment of advanced testicular germ cell tumors has changed over the past 30 years, with long-term survival now achieved in the majority of patients. Clinicians need to be familiar with the available treatment regimens for testicular cancer and their associated toxic effects.To review the treatments used for advanced testicular germ cell tumors and their associated short-term and long-term complications.A search was performed of all English-language literature (1966 to October 2007) within the MEDLINE database using the terms neoplasms, germ cell, or embryonal or testicular neoplasms restricted to humans, drug therapy, complications, and mortality. The Cochrane Register of Controlled Trials Databases (through October 2007) was also searched using the terms testicular cancer or germ cell tumors. Bibliographies were reviewed to extract other relevant articles. One hundred eighty-six articles were selected based on pertinence to advanced testicular cancer treatment, associated complications, and late relapses with an emphasis on randomized controlled trials.The treatment of advanced testicular germ cell tumors with cisplatin combination chemotherapy is based on risk stratification (good, intermediate, or poor prognosis) according to pretreatment clinical features of prognostic value. Clinical trials have demonstrated that approximately 90% of patients classified as having a good prognosis achieve a durable complete remission to either 4 cycles of etoposide and cisplatin or 3 cycles of cisplatin, etoposide, and bleomycin. Complete responses are achieved less frequently for patients with intermediate- and poor-risk germ cell tumors, in whom 4 cycles of bleomycin, etoposide, and cisplatin remains the standard of care. Second- and third-line programs, including high-dose chemotherapy, also have curative potential. Chronic toxicities associated with therapy include cardiovascular disease, infertility, and secondary malignancies. Late relapses may also occur.Clinical trials have led to evidence-based treatment recommendations for advanced testicular cancer based on risk stratification. Clinicians should be familiar with the potential complications of these therapies.