tbuckley/cabot-search huggingface dataset:
Obstacles to answering doctors' questions about patient care with evidence: qualitative study
Authors: J. W Ely
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To describe the obstacles encountered when attempting to answer doctors9 questions with evidence. <b>Design:</b> Qualitative study. <b>Setting:</b> General practices in Iowa. <b>Participants:</b> 9 academic generalist doctors, 14 family doctors, and 2 medical librarians. <b>Main outcome measure:</b> A taxonomy of obstacles encountered while searching for evidence based answers to doctors9 questions. <b>Results:</b> 59 obstacles were encountered and organised according to the five steps in asking and answering questions: recognise a gap in knowledge, formulate a question, search for relevant information, formulate an answer, and use the answer to direct patient care. Six obstacles were considered particularly salient by the investigators and practising doctors: the excessive time required to find information; difficulty modifying the original question, which was often vague and open to interpretation; difficulty selecting an optimal strategy to search for information; failure of a seemingly appropriate resource to cover the topic; uncertainty about how to know when all the relevant evidence has been found so that the search can stop; and inadequate synthesis of multiple bits of evidence into a clinically useful statement. <b>Conclusions:</b> Many obstacles are encountered when asking and answering questions about how to care for patients. Addressing these obstacles could lead to better patient care by improving clinically oriented information resources. <h3>What is already known on this topic</h3> Doctors are encouraged to search for evidence based answers to their questions about patient care but most go unanswered Studies have not defined the obstacles to answering questions in a systematic manner A comprehensive description of such obstacles has not been presented <h3>What this study adds</h3> Fifty nine obstacles were found while attempting to answer clinical questions with evidence; six were particularly salient The obstacles were comprehensively described and organised
Distinct roles of class I PI3K isoforms in multiple myeloma cell survival and dissemination
Authors: I Sahin, M Moschetta, Y Mishima, S V Glavey, B Tsang, F Azab, S Manier, Y Zhang, P Maiso, A Sacco, A K Azab, A M Roccaro, I M Ghobrial
Journal: Blood Cancer Journal (2014)

Distinct roles of class I PI3K isoforms in multiple myeloma cell survival and dissemination
Pressure drop across artificially induced stenoses in the femoral arteries of dogs.
Authors: D F Young, N R Cholvin, A C Roth
Journal: Circulation Research (1975)

Stenoses were artificially induced in 13 large mongrel dogs by implanting small hollow cylindrical plugs in their femoral arteries. The instantaneous pressure drop across the stenosis and the flow rate were measured for a series of stenoses varying in severity from 52.3 to 92.2%. Mean pressure drops ranged from approximately 2 to 30 mm Hg with peak pressure drops ranging from 9 to 53 mm Hg. The pressure drop could be estimated from a relatively simple equation that was originally developed for flow through model stenoses. With this equation, the effects of several factors that contribute to the pressure drop, including stenosis size and shape, artery lumen diameter, blood density, blood viscosity, and velocity and acceleration of flow, could be clearly delineated. For severe stenoses, unsteady flow effects were small and flow could be treated as quasi-steady. Calculations based on data obtained from the dog experiments revealed that the mean pressure drop across a stenosis increased nonlinearly with percent stenosis and showed quantitatively that the value of critical stenosis decreased with increasing demand for blood flow.
Granulomatous lesions of the homolateral limb after previous mastectomy
Authors: A. Virgili, C. Maranini, A. Califano
Journal: British Journal of Dermatology (2002)

Journal Article Granulomatous lesions of the homolateral limb after previous mastectomy Get access A. Virgili, A. Virgili Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy Annarosa Virgili. E‐mail: vri@unife.it Search for other works by this author on: Oxford Academic Google Scholar C. Maranini, C. Maranini Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Califano A. Califano Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 5, 1 May 2002, Pages 891–894, https://doi.org/10.1046/j.1365-2133.2002.04647.x Published: 01 May 2002 Article history Accepted: 25 October 2001 Published: 01 May 2002
Accessory Spleen in Hodgkin's Disease
Authors: Gerald O. Strauch
Journal: JAMA (1979)

To the Editor.—  The problem of dealing with accessory spleens in patients undergoing laparotomy for abdominal staging of Hodgkin's disease, addressed by Jacobson and Reynolds (240:2081, 1978), seems worthy of further comment in view of two recent developments.  The first of these is the growing realization that the problem of postsplenectomy sepsis in patients with Hodgkin's disease who have undergone total splenic ablation is of such magnitude that reappraisal of the value of total splenectomy for some patients seems in order. An assessment of the literature published since the risk of postsplenectomy sepsis in these patients became manifest indicates that the risk may range from about 10% overall 1 to more than 20% in patients who require aggressive multimodal therapy for their disease. 2 Since the mortality of patients with postsplenectomy sepsis remains extremely high, regardless of therapy once sepsis occurs, and since measures for prevention of postsplenectomy sepsis have
Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction
Authors: Anique Ducharme, Stefan Frantz, Masanori Aikawa, Elena Rabkin, Merry Lindsey, Luis E. Rohde, Frederick J. Schoen, Ralph A. Kelly, Zena Werb, Peter Libby, Richard T. Lee
Journal: Journal of Clinical Investigation (2000)

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI.
Insulin Induces the Release of Vasodilator Compounds From Platelets by a Nitric Oxide–G Kinase–VAMP-3–dependent Pathway
Authors: Voahanginirina Randriamboavonjy, Jürgen Schrader, Rudi Busse, Ingrid Fleming
Journal: The Journal of Experimental Medicine (2004)

Insulin-induced vasodilatation is sensitive to nitric oxide (NO) synthase (NOS) inhibitors. However, insulin is unable to relax isolated arteries or to activate endothelial NOS in endothelial cells. Since insulin can enhance platelet endothelial NOS activity, we determined whether insulin-induced vasodilatation can be attributed to a NO-dependent, platelet-mediated process. Insulin failed to relax endothelium-intact rings of porcine coronary artery. The supernatant from insulin-stimulated human platelets induced complete relaxation, which was prevented by preincubation of platelets with a NOS inhibitor, the soluble guanylyl cyclase inhibitor, NS 2028, or the G kinase inhibitor, KT 5823, and was abolished by an adenosine A2A receptor antagonist. Insulin induced the release of adenosine trisphosphate (ATP), adenosine, and serotonin from platelet-dense granules in a NO-dependent manner. This response was not detected using insulin-stimulated platelets from endothelial NOS−/− mice, although a NO donor elicited ATP release. Insulin-induced ATP release from human platelets correlated with the association of syntaxin 2 with the vesicle-associated membrane protein 3 but was not associated with the activation of αIIbβ3 integrin. Thus, insulin elicits the release of vasoactive concentrations of ATP and adenosine from human platelets via a NO–G kinase–dependent signaling cascade. The mechanism of dense granule secretion involves the G kinase–dependent association of syntaxin 2 with vesicle-associated membrane protein 3.
Effect of Ca ++ antagonists and ACE inhibitors on the elastic properties of the aorta in essential hypertension: different mechanisms of action
Authors: C. Vlachopoulos, C. Stefanadis, E. Tsiamis, C. Tsioufis, K. Toutouzas, C. Stratos, J. Demellis, L. Diamantopoulos, N. Giatrakos, C. Pitsavos, P. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
T‐lymphoid blast crisis in chronic myeloid leukemia
Authors: S. H. Advani, H. Malhotra, P. R. Kadam, R. S. Iyer, G. Nanjangud, B. Balsara, T. Saikia, R. Gopal, C. N. Nair
Journal: American Journal of Hematology (1991)

Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differentiation frequently occurs along B-cell lineage. We report four patients of CML who terminated in T-cell extramedullary BC in lymph nodes after a variable duration of chronic phase. The T-lineage was established by characteristic cytochemical staining and reactivity with a panel of anti-T-cell monoclonal antibodies. All four cases were Philadelphia (Ph) chromosome positive and demonstrated the Ph chromosome and associated anomalies (extra Ph, +19) in the lymph nodes. Our data adds to the growing evidence that CML is a disorder of the common stem cell from which T, B, and myeloid precursors originate.
Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo.
Authors: R D Rossen, L H Michael, A Kagiyama, H E Savage, G Hanson, M A Reisberg, J N Moake, S H Kim, D Self, S Weakley
Journal: Circulation Research (1988)

To evaluate whether ischemic myocardium releases molecules that react with the first component of complement, we studied cardiac lymph from eight dogs before and at intervals after coronary artery occlusion and reperfusion. Before occlusion, the dogs were injected intravenously with radiolabeled human C1q. Labeled C1q could be detected in the cardiac lymph within minutes following injection. Rabbit antisera, prepared against substances precipitated from postreprefusion cardiac lymph by anti-human C1q, also reacted with specific constituents of isolated cardiac sarcoplasmic reticulum and mitochondria. To evaluate whether mitochondria are the source of these C1q-binding proteins, we isolated intramyofibrillar and subsarcolemmal mitochondria from canine heart and incubated sonicates of these with purified C1q, immobilized on nitrocellulose. Molecules bound to the immobilized C1q were removed with 0.1% sodium dodecyl sulfate, fractionated under reducing conditions by polyacrylamide gel electrophoresis, and transferred electrophoretically to nitrocellulose paper. Antisera prepared against postreperfusion lymph reacted with a 31,000-32,000-dalton protein in these nitrocellulose paper replicas. Since this protein originates from mitochondria, binds to C1q, and is recognized by antibodies made against postreperfusion lymph, this protein is likely to be one of the subcellular constituents that, upon release from ischemic cells, activates the complement cascade. To evaluate the clinical relevance of these observations, we tested sera from 53 patients obtained 48-72 hours after hospitalization for suspected myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial Oxygen Consumption During Ventricular Contraction and Relaxation
Authors: R. Grier MONROE
Journal: Circulation Research (1964)

Determinations of left ventricular oxygen consumption were made in the isolated heart of a dog while the ventricle performed work by compressing air. In the described preparation the air compressed by the ventricle could be rapidly released and the ventricular pressure pulse repeatedly interrupted at specific points during its cycle. Upon interrupting the pressure pulse at its peak there was a 10% increase in peak pressure that appeared in the subsequent four to five beats. When the intraventricular pressure was released at various points during its ascent to peak pressure, left ventricular oxygen consumption could be correlated with both the pressure, at which it was interrupted, and the area under the pressure pulse. When the oxygen consumed by a ventricle developing a full pressure pulse was compared to that of a ventricle in which the intraventricular pressure was released at its peak-land when the peak systolic pressure of the two compared pulses were equal-then the oxygen consumed by the ventricle when the pulse was interrupted averaged 91% of that when the pulse was full. These studies indicate that by the time the pressure pulse has reached its peak, myocardial oxygen consumption has been largely determined, and that the oxygen cost of the ventricular relaxation is small.
Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis
Authors: Rafael de Cid, Eva Riveira-Munoz, Patrick L J M Zeeuwen, Jason Robarge, Wilson Liao, Emma N Dannhauser, Emiliano Giardina, Philip E Stuart, Rajan Nair, Cynthia Helms, Georgia Escaramís, Ester Ballana, Gemma Martín-Ezquerra, Martin den Heijer, Marijke Kamsteeg, Irma Joosten, Evan E Eichler, Conxi Lázaro, Ramón M Pujol, Lluís Armengol, Gonçalo Abecasis, James T Elder, Giuseppe Novelli, John A L Armour, Pui-Yan Kwok, Anne Bowcock, Joost Schalkwijk, Xavier Estivill
Journal: Nature Genetics (2009)
The Effect of Proton Pump Inhibitor on the Exhaled Breath Condensate pH and QOL in QUEST Questionnaire-Positive Asthmatics
Authors: T. Yano, H. Nagase, J. Nakano, H. Yoshihara, K. Yamamura, S. Ueki, O. Ohbayashi, M. Nakajima, T. Adachi, K. Ohta
Journal: Journal of Allergy and Clinical Immunology (2007)
Fluorescence Microangiography for Quantitative Assessment of Peritubular Capillary Changes after AKI in Mice
Authors: Rafael Kramann, Mari Tanaka, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2014)

AKI predicts the future development of CKD, and one proposed mechanism for this epidemiologic link is loss of peritubular capillaries triggering chronic hypoxia. A precise definition of changes in peritubular perfusion would help test this hypothesis by more accurately correlating these changes with future loss of kidney function. Here, we have adapted and validated a fluorescence microangiography approach for use with mice to visualize, analyze, and quantitate peritubular capillary dynamics after AKI. A novel software-based approach enabled rapid and automated quantitation of capillary number, individual area, and perimeter. After validating perfusion in mice with genetically labeled endothelia, we compared peritubular capillary number and size after moderate AKI, characterized by complete renal recovery, and after severe AKI, characterized by development of interstitial fibrosis and CKD. Eight weeks after severe AKI, we measured a 40%±7.4% reduction in peritubular capillary number (P<0.05) and a 36%±4% decrease in individual capillary cross-sectional area (P<0.001) for a 62%±2.2% reduction in total peritubular perfusion (P<0.01). Whereas total peritubular perfusion and number of capillaries did not change, we detected a significant change of single capillary size following moderate AKI. The loss of peritubular capillary density and caliber at week 8 closely correlated with severity of kidney injury at day 1, suggesting irreparable microvascular damage. These findings emphasize a direct link between severity of acute injury and future loss of peritubular perfusion, demonstrate that reduced capillary caliber is an unappreciated long-term consequence of AKI, and offer a new quantitative imaging tool for understanding how AKI leads to future CKD in mouse models.
Asthma: managing the acute attack
Authors: M K. Thompson
Journal: BMJ (1981)

oxygen cylinders were supplied by area health authorities (via hospitals) in 54°,, of all centres prescribing portable oxygen.Other centres relied on charities or had patients buyingtheir own.Both the issuing and financing of portable oxygen on a national level also seems to be inconsistent.The Chronically Sick and Disabled Persons Act 1970, chapter 44, section 22, stipulates that the Secretary of State should compile an annual report on "progress in research and development work in relation to equipment that might increase the range of activities and independence or well-being of disabled persons, and in particular such equipment that might improve the indoor and outdoor mobility of such persons."In this respect the benefits of portable oxygen in certain patients, as shown by Woodcock et al,' should perhaps be further considered, and be made more readily available throughout the country.
Reducing the impact of myocardial ischaemia/reperfusion injury
Authors: H. M. Piper, D. Garcia-Dorado
Journal: Cardiovascular Research (2012)

It seems surprising that more than five decades of intense biochemical and molecular research on a leading cause of death and disability globally—ischaemic myocardial injury/myocardial infarction—and the spending of huge sums of money have achieved relatively little in the prevention of cell death secondary to ischaemia. The greatest progress has been made in methods to mechanically or chemically re-open acutely occluded coronary arteries and in increasingly better logistics of pre-hospital treatment and patient transport to hospitals providing this kind of therapy. This has resulted in a very important reduction in mortality among patients with acute myocardial infarction. The understanding of the pathological mechanism of ischaemic cell injury in the heart has also grown impressively, but much of this knowledge concerns the initiation of cell injury as a result of oxygen and energy deprivation, accumulating cellular ion imbalance, proteolytic activation, cell swelling, and similar mechanisms. The effects on ischaemic cell injury of a very effective protective regimen that is provided by the procedure of preconditioning applied prior to ischaemia are also impressive. But apart from the limited applicability of this therapeutic wisdom in cardiac surgery, nothing practical has come out of this knowledge as the much more frequent clinical situation is the one in which cardiac ischaemia is already manifest at the time the patient seeks medical help. There is encouraging preliminary evidence that ischaemic and pharmacological conditioning at the time of reperfusion may also be protective, but the impact of these approaches on clinical practice is negligible.

Having made this point, we think it is fortunate that researchers have not given up early on analysing the cellular and subcellular changes in ischaemic myocardial cells. As it turned out, many different mechanisms play a role in cardiomyocyte injury when the ischaemic tissue is reperfused. This is not a trivial finding, since …
Endotoxin contamination causes neutrophilia following pulmonary allergen challenge.
Authors: L W Hunt, G J Gleich, T Ohnishi, D A Weiler, E S Mansfield, H Kita, S Sur
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen extracts were contaminated with endotoxin. The extracts used for challenge in the first four patients tested positive for bacterial endotoxin in a limulus amebocyte lysate assay. Rechallenge of one patient from the first group with a comparable dose of an endotoxin-free extract and SBP with endotoxin-free extract in five additional patients resulted in preferential recruitment of eosinophils rather than neutrophils. The number of neutrophils recovered from the challenged segments in the patients challenged with endotoxin-free extract was significantly less than that observed in the first four patients. Taken together, these observations suggest that neutrophil recruitment in the 24-h BAL fluids from the first four patients was probably due to endotoxin contamination of the allergen extract. We caution investigators that endotoxin contamination of allergen extract may alter the cellular inflammation during the late airway response following allergen challenge.
Respiratory events during long term noninvasive positive pressure ventilation in children: Clinical implications and detection of events
Authors: Valeria Calderelli, Jean Christian Borel, Sonia Khirani, Adriana Ramirez, Renato Cutrera, Jean Louis Pepin, Brigitte Fauroux
Journal: European Respiratory Journal (2012)

OBJECTIVE

The aims of the study were (1) to describe the respiratory events during noninvasive positive pressure ventilation (NPPV) and, (2) to analyze the clinical consequences.

METHOD

Nocturnal polygraphic (PG) recordings were performed in stable patients. Respiratory events were scored using the SomnoNIV Group definitions [1]. The consequences of an event i.e. a fall of ≥ 3% of pulse oximetry (SpO2) and/or a ≥ 30% decrease in pulse rate amplitude (respiratory autonomic micro-arousals: RAM) were described.

RESULTS

PG tracings of 27 patients (13 boys, age range 1-18) were analysed: neuromuscular disease (n=7), obstructive sleep apnea (n=8) and lung disease (n=12). Unintentional leaks, partial or total upper airway obstruction without reduction of ventilatory drive, a decrease in ventilatory drive, mixed events, and patient ventilator asynchronies were observed in 61%; 37%; 28%; 7%; 53% of the patients, respectively. These events were associated with a decrease of SpO2 in 21%; 37%; 18%; 4%; 12% of the patients respectively, and with a RAM in 38%; 27%; 8%; 3%; 32% of the patients respectively. The mean number of type of events per patient was 1.8±1.1. For a given patient, there was a predominant event representing 87 ± 10% of total time with respiratory events. The median duration spend in respiratory event was 39% (range 0.7 to 92%) of total recording time. Of the patients with a minimal nocturnal SpO2 >90% and a PtcCO2 <50mmHg, 12 (44%) had at least one respiratory event.

CONCLUSION

Respiratory events are common in stable children treated with long term NPPV and can be associated with desaturations and/or RAM.

1. Gonzalez J et al. Thorax 2011.