tbuckley/cabot-search huggingface dataset:
What is the evidence that postgraduate teaching in evidence based medicine changes anything? A systematic review
Authors: Arri Coomarasamy, Khalid S Khan
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effects of standalone versus clinically integrated teaching in evidence based medicine on various outcomes in postgraduates. <b>Design</b> Systematic review of randomised and non-randomised controlled trials and before and after comparison studies. <b>Data sources</b> Medline, Embase, ERIC, Cochrane Library, DARE, HTA database, Best Evidence, BEME, and SCI. <b>Study selection</b> 23 studies: four randomised trials, seven non-randomised controlled studies, and 12 before and after comparison studies. 18 studies (including two randomised trials) evaluated a standalone teaching method, and five studies (including two randomised trials) evaluated a clinically integrated teaching method. <b>Main outcome measures</b> Knowledge, critical appraisal skills, attitudes, and behaviour. <b>Results</b> Standalone teaching improved knowledge but not skills, attitudes, or behaviour. Clinically integrated teaching improved knowledge, skills, attitudes, and behaviour. <b>Conclusion</b> Teaching of evidence based medicine should be moved from classrooms to clinical practice to achieve improvements in substantial outcomes.
Anomalous Left Coronary Artery from Pulmonary Artery
Authors: LOWELL W. PERRY, LEWIS P. SCOTT
Journal: Circulation (1970)

Anomalous origin of the left coronary artery from the pulmonary artery has been noted in 11 patients at Children's Hospital of the District of Columbia from 1946 to 1969. Four of our cases plus 40 in the literature have been reported with complete catheterization data. These 44 infants and children can be divided into three groups (A, B, and C) according to the magnitude of the shunt at pulmonary artery level. The type of treatment in infants and children with anomalous left coronary artery and increased oxygen saturation in the pulmonary artery at the time of catheterization (group A) appears to be immaterial, as all have survived. Mortality rates in patients with left-to-right shunts not large enough to be detected by oxygen studies (group B) indicate no significant difference in those treated medically or surgically; hence, if possible, surgery should be delayed in this group until after 1 to 2 years of age when surgical mortality is negligible. In patients with filling of the left coronary artery from the pulmonary artery (group C), direct anastomosis of the anomalous left coronary artery to the aorta seems to be the only therapeutic recourse. To date, there are insufficient data to indicate the efficacy of direct anastomosis of the anomalous left coronary artery to the aorta in the sick infant.
VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo
Authors: Elizabeth A Harrington, David Bebbington, Jeff Moore, Richele K Rasmussen, Abi O Ajose-Adeogun, Tomoko Nakayama, Joanne A Graham, Cecile Demur, Thierry Hercend, Anita Diu-Hercend, Michael Su, Julian M C Golec, Karen M Miller
Journal: Nature Medicine (2004)
Impairment of endothelium-independent vasodilation in patients with hypercalcemia
Authors: T Neunteufl
Journal: Cardiovascular Research (1998)

Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT.Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz).NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017).Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.
Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart
Authors: Hyun-Jai Cho, Namho Lee, Ji Yoon Lee, Yong Jin Choi, Masaaki Ii, Andrea Wecker, Jin-Ok Jeong, Cynthia Curry, Gangian Qin, Young-sup Yoon
Journal: The Journal of Experimental Medicine (2007)

Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury.
LAB ON A CD
Authors: Marc Madou, Jim Zoval, Guangyao Jia, Horacio Kido, Jitae Kim, Nahui Kim
Journal: Annual Review of Biomedical Engineering (2006)

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.
General Practice Observed: Survey of General Practice Records
Authors: K. S. Dawes
Journal: BMJ (1972)

A study of a sample of records from eight general practices showed that 10% of patients' ages were not recorded, that 99% of males had no indication of their marital state, and 60% did not have an occupation recorded. In recording of disease episodes a diagnosis was recorded in a little over half of the episodes and was the only recorded item in 10% of records. The recording of the therapeutic agent used was the most frequently recorded item, occurring in 70% of episodes, but the amount prescribed was recorded in only one-quarter of the episodes and the dosage in less than one-fifth. Less than half of the episodes had any symptoms recorded and only one-third had a physical sign recorded.
Endobronchial tuberculosis with expectoration of tracheal cartilages
Authors: M.j Park, I.s Woo, J.w Son, S.j Lee, D.g Kim, E.k Mo, M.g Lee, I.g Hyun, K.s Jung
Journal: European Respiratory Journal (2000)

A case of endotracheal tuberculosis with expectorations of the lateral one-third of the multiple tracheal cartilages is reported. Fibreoptic bronchoscopy revealed caseous materials and loosening of the tracheal cartilages. The patient expectorated cartilaginous material several times before and after fibreoptic bronchoscopy. In spite of the loss of tracheal cartilages, tracheal lumen was maintained with a mild airflow limitation. The remaining two-thirds of the tracheal cartilage rings seemed to be strong enough to support the tracheal lumen opening during the respiratory cycle. Although rare, expectoration of bronchial cartilage can be one of the clinical features of endobronchial tuberculosis.
HETEROGENEITY OF THE EFFECTOR CELLS IN THE CYTOTOXIC REACTION AGAINST ALLOGENEIC LYMPHOMA CELLS
Authors: James Forman, Sven Britton
Journal: The Journal of Experimental Medicine (1973)

The cytotoxic effect of spleen cells from H-2 allogeneic mice was tested in vitro against an A strain leukemia (YAC) labeled with [(125)I]iododeoxyuridine. After the mice were primed with tumor cells, significant and specific H-2 immunity was detected on day 3 and peak cytotoxicity was observed between 7 and 14 days after priming. Two effector cells appear to be involved in the host response, because spleens taken from mice soon after priming were not sensitive to antitheta sera and complement while those taken during the peak stages of the response showed a marked reduction in cytotoxicity after treatment. Macrophages were not involved, since removal of these cells by the carbonyl iron method did not result in any reduction in cytotoxicity. Immune serum that was capable of inducing cell-mediated cytotoxicity in normal spleen cell populations also augmented cytotoxicity of spleen cells taken from mice primed 3 days previously. However, when spleen cells were taken from mice during the peak phase of the immune response, the same serum at the same dilutions inhibited the preexisting cytotoxicity. A difference was also detected in the killing efficiencies between early and late immune cells.
Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha.
Authors: S R McColl, R Paquin, C Ménard, A D Beaulieu
Journal: The Journal of Experimental Medicine (1992)

Neutrophils, an abundant cell type at sites of inflammation, have the ability to produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). In this study, we have examined the ability of human neutrophils to produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both the in vitro and in vivo effects of IL-1, its production by large numbers of tissue-invading neutrophils might provide a mechanism by which the effects of IL-1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra and a cDNA probe encoding for this protein, we were able to show that neutrophils constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha, IL-1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils. None of a large array of other potent neutrophil agonists were found to affect the production of IL-1Ra by neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and TNF-alpha-activated cells, this difference was reduced to values between four- and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5-ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a factor of at least 100, an observation that is in agreement with the reported amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1. Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms of IL-1Ra synthesis, indicating that the in vitro observations made in this study are likely to occur in an inflammatory setting in vivo.
Seldinger chest drain insertion: simpler but not necessarily safer
Authors: N. A Maskell, A. Medford, F. V Gleeson
Journal: Thorax (2009)

An important next step would be to evaluate the natural history of children who successfully underwent surgical treatment of OSA.Many studies suggest that a significant number of children have incomplete resolution of OSA after surgery, but we do not know how many children worsen over time.In summary, this is an important first study but much needs to be done before we can decide whether watchful waiting is a valid long-term management plan for children with mild OSA.
PDGF-D and Renal Disease
Authors: Jürgen Floege, Frank Eitner, Claudia van Roeyen, Tammo Ostendorf
Journal: Journal of the American Society of Nephrology (2003)

Life in the platelet-derived growth factor (PDGF) world used to be simple for the last twenty years. The system consisted of two PDGF chains, PDGF-A and -B, that are secreted as homodimers or heterodimers and bind to dimeric PDGF receptors composed of α- and/or β-chains. Whereas PDGF-A binds to
Asymmetric Evolution in Two Fish-Specifically Duplicated Receptor Tyrosine Kinase Paralogons Involved in Teleost Coloration
Authors: Ingo Braasch, Walter Salzburger, Axel Meyer
Journal: Molecular Biology and Evolution (2006)

The occurrence of a fish-specific genome duplication (FSGD) in the lineage leading to teleost fishes is widely accepted, but the consequences of this event remain elusive. Teleosts, and the cichlid fishes from the species flocks in the East African Great Lakes in particular, evolved a unique complexity and diversity of body coloration and color patterning. Several genes involved in pigment cell development have been retained in duplicate copies in the teleost genome after the FSGD. Here we investigate the evolutionary fate of one of these genes, the type III receptor tyrosine kinase (RTK) colony-stimulating factor 1 receptor (csf1r). We isolated and shotgun sequenced two paralogous csf1r genes from a bacterial artificial chromosome library of the cichlid fish Astatotilapia burtoni that are both linked to paralogs of the pdgfr beta gene, another type III RTK. Two pdgfr beta-csf1r paralogons were also identified in the genomes of pufferfishes and medaka, and our phylogenetic analyses suggest that the pdgfr beta-csf1r locus was duplicated during the course of the FSGD. Comparisons of teleosts and tetrapods suggest asymmetrical divergence at different levels of genomic organization between the teleost-specific pdgfr beta-csf1r paralogons, which seem to have evolved as coevolutionary units. The high-evolutionary rate in the teleost B-paralogon, consisting of csf1rb and pdgfr betab, further suggests neofunctionalization by functional divergence of the extracellular, ligand-binding region of these cell-surface receptors. Finally, we hypothesize that genome duplications and the associated expansion of the RTK family might be causally linked to the evolution of coloration in vertebrates and teleost fishes in particular.
Risks to Relatives in Genomic Research: A Duty to Warn?
Authors: Yvonne Bombard, Kenneth Offit, Mark E. Robson
Journal: The American Journal of Bioethics (2012)

Click to increase image sizeClick to decrease image size Acknowledgments We acknowledge support from the Robert and Kate Niehaus Clinical Cancer Genetics Initiative and the Canadian Institutes of Health Research (CIHR) for a postdoctoral fellowship awarded to Dr. Yvonne Bombard.
The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis
Authors: Jasper H. Smalberg, Edith Koehler, Sarwa Darwish Murad, Aurelie Plessier, Susana Seijo, Jonel Trebicka, Massimo Primignani, Moniek P. M. de Maat, Juan-Carlos Garcia-Pagan, Dominique C. Valla, Harry L. A. Janssen, Frank W. G. Leebeek
Journal: Blood (2011)
Abstract 339: Heterozygous Disruption of Drp1 Enhances Myocardial Injury in Response to Ischemia/Reperfusion via Inhibition of Mitophagy
Authors: Yoshiyuki Ikeda, Peiyong Zhai, Mitsuru Ohishi, Junichi Sadoshima
Journal: Circulation Research (2014)

Mitochondrial fission and fusion are essential for maintaining mitochondrial quality control. However, their role in stress resistance remains unknown. Since Dynamin-related protein 1 (Drp1) plays an essential role in mediating mitochondrial fission, we used cardiac-specific heterozygous Drp1 KO (Drp1-hetCKO) mice whose cardiac function is normal at 12 weeks of age. In order to evaluate the role of Drp1 in mediating stress resistance, 12-week-old Drp1-hetCKO and control (Ctr) mice were subjected to myocardial ischemia (30 min)/reperfusion (24 hours) (I/R). I/R injury increased the translocation of Drp1 from cytosol to mitochondria in Ctr mice, whereas this translocation was attenuated in Drp1-hetCKO mice.The infarct size/area at risk after I/R was significantly greater in Drp-1 hetero KO mice than in control mice (55.2 ± 3.0 vs. 40.2 ± 1.6%). Electron microscopic analyses showed that I/R significantly decreased mitochondrial mass and increased the number of autophagosomes containing mitochondria in control mice. However, these changes were significantly attenuated in Drp1-hetCKO mice, suggesting that endogenous Drp1 mediates mitochondrial fission and mitophagy after I/R (Relative mitochondrial mass, Ctr, baseline: 1.0±0.3, I/R: 0.7±0.4; Drp1-hetCKO, baseline: 1.8±0.3, I/R: 1.7±0.3). We also examined mitophagy using mitochondria-targeted Keima fluorescence. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH states, respectively. The maturation of autophagosomes to autolysosomes can be monitored by measuring the fluorescence of mitochondria-targeted Keima. Fluorescent dots with high ratios of 560/440, indicating mitophagy, were significantly increased after GD in sh-scramble-transduced CMs (GD: 28.6±4.2, control 2.3±1.0 dots/cell, p&lt;0.01) but not in sh-Drp1-transduced CMs (GD: 2.4±1.8, control 3.2±1.6 dots/cell, not significant), suggesting that GD stimulates mitophagy but that this is inhibited when Drp-1 is downregulated. These results suggest that endogenous Drp1 play an essential role in mediating mitochondrial fission and mitophagy, which in turn play an essential role in mediating myocardial protection in response to I/R.
Role of cyclic guanosine monophosphate and K<sup>+</sup>channels as mediators of the mesenteric vascular hyporesponsiveness in portal hypertensive rats
Authors: Noemí M. Atucha, Clara M. Ortíz, Lourdes A. Fortepiani, Francisco M. Ruiz, Concepción Martínez, Joaquín García-Estañ
Journal: Hepatology (1998)

The mechanisms mediating the hyporesponsiveness to vasoconstrictors in portal hypertension are not completely established. In the present study, we evaluated the role of cyclic guanosine monophosphate (cGMP) and potassium channels as contributors to the pressor hyporesponsiveness to methoxamine (MTX) of the mesenteric vascular bed of portal vein-ligated (PVL) hypertensive rats. In basal conditions, and compared with sham-operated control rat (SHAM) vessels, PVL preparations showed a blunted pressor response (maximum: 39.3 +/- 6.1 vs. 94.5 +/- 8.9 mm Hg), which increased by pretreatment with methylene blue (MB), a guanylate cyclase inhibitor (118.7 +/- 8.9 vs. 152.0 +/- 10.0, respectively), and even more with the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine (NNA) (159.9 +/- 7.4 vs. 194.1 +/- 5.7, respectively), suggesting that NO acts through cGMP-dependent and independent mechanisms. In all cases, however, the pressor responses of PVL vessels were lower than those of SHAM. Pretreatment of the vessels with the potassium channel inhibitors, tetraethylammonium (TEA), glibenclamide (GLB), or charybdotoxin (CHX), did not improve the reduced pressor responses of the PVL rats. However, when the preparations were simultaneously pretreated with MB and TEA or with NNA and TEA, the pressor responses were potentiated with respect to groups treated with MB or NNA alone, and the differences between PVL and SHAM vessels were completely corrected. These data suggest that both NO and potassium channels mediate the vascular hyporesponsiveness to methoxamine of the PVL mesenteric vasculature. Our results also disclose that NO blunts the pressor response of the PVL vessels by a dual mechanism of action, through activation of potassium channels and through the formation of cGMP. Finally, the NO-independent component mediated by potassium channels can be only seen when the main cGMP-NO component is inactivated. In conclusion, both cGMP and potassium channels mediate the vascular hyporesponsiveness to MTX of the mesenteric bed of portal hypertensive rats.
Calcium Antagonists for Hypertrophic Cardiomyopathy
Authors: Samuel Vaisrug
Journal: JAMA (1980)

Contrasting with the cornucopia of synonyms for hypertrophic cardiomyopathy, the scarcity of its therapeutic options is striking indeed. The only alternative to propranolol hydrochloride for the relief of obstruction to the left ventricular outflow tract has been septal myotomy-myectomy. When β-adrenergic blockade proves ineffective, as it not infrequently does, and if surgery is contraindicated, the patient has nowhere to turn for help. Recent trials with a calcium antagonist, verapamil, hold out a strong hope for a pharmacologic alternative. In an earlier communication (1976), Kaltenbach and associates<sup>1</sup>reported impressive symptomatic improvement in patients treated with oral verapamil for an average of 12 months. In a later report<sup>2</sup>on their expanded study, this group of investigators described favorable results in 40 patients treated for three to 56 months (mean, 26 months) with verapamil in oral dosages of 480 to 720 mg/day. Not only did the drug relieve symptoms and improve