tbuckley/cabot-search huggingface dataset:
A New Look at Cardiac Exercise Testing
Authors: Gregory D. Curfman, L. David Hillis
Journal: New England Journal of Medicine (2003)

Since the introduction of treadmill exercise testing by Robert Bruce five decades ago, graded exercise testing has been a cornerstone of diagnostic procedures for coronary artery disease. An article in this issue of the Journal from the Cleveland Clinic Foundation (pages 781–790), along with a previous Journal article from the same group,1 takes a new look at this frequently used test, focusing attention on the recovery period after the completion of exercise. Together, these studies show that careful observations during the period immediately after exercise provide important diagnostic and prognostic information; in so doing, they bring a new dimension to . . .
Surfactant and pulmonary blood flow distributions following treatment of premature lambs with natural surfactant.
Authors: A Jobe, M Ikegami, H Jacobs, S Jones
Journal: Journal of Clinical Investigation (1984)

Prematurely delivered lambs were treated with radiolabeled natural surfactant by either tracheal instillation at birth and before the onset of mechanical ventilation, or after 23 +/- 1 (+/- SE) min of mechanical ventilation. Right ventricular blood flow distributions, left ventricular outputs, and left-to-right ductal shunts were measured with radiolabeled microspheres. After sacrifice, the lungs of lambs receiving surfactant at birth inflated uniformly with constant distending pressure while the lungs of lambs treated after a period of ventilation had aerated, partially aerated, and atelectatic areas. All lungs were divided into pieces which were weighed and catalogued as to location. The amount of radiolabeled surfactant and microsphere-associated radioactivity in each piece of lung was quantified. Surfactant was relatively homogenously distributed to pieces of lung from lambs that were treated with surfactant at birth; 48% of lung pieces received amounts of surfactant within +/- 25% of the mean value. Surfactant was preferentially recovered from the aerated pieces of lungs of lambs treated after a period of mechanical ventilation, and the distribution of surfactant to these lungs was very nonhomogeneous. Right ventricular blood flow distributions to the lungs were quite homogeneous in both groups of lambs. However, in 8 of 12 lambs, pulmonary blood flow was preferentially directed away from those pieces of lung that received relatively large amounts of surfactant and toward pieces of lung that received less surfactant. This acute redirection of pulmonary blood flow distribution may result from the local changes in compliances within the lung following surfactant instillation.
Transepithelial water flow regulates apical membrane retrieval in antidiuretic hormone-stimulated toad urinary bladder.
Authors: H W Harris, J B Wade, J S Handler
Journal: Journal of Clinical Investigation (1986)

Antidiuretic hormone (ADH) increases the osmotic water permeability (Posm) of toad urinary bladder. This increase is believed to be produced by fusion of intracellular vesicles called aggrephores with the granular cell apical plasma membrane. Aggrephores contain intramembrane particle aggregates postulated to be water channels. ADH-stimulated Posm is decreased by osmotic gradient exposure, which is termed flux inhibition. We studied flux inhibition by exposing ADH-stimulated bladders to various osmotic gradients. Osmotic water flow was initially proportional to the applied osmotic gradient, but Posm decreased with time. Ultrastructural and quantitative studies of endocytosis demonstrate that apical membrane retrieval was a direct function of the transepithelial osmotic gradient. Posm remained unchanged when apical membrane retrieval was blocked by incubation of bladders at 2 degrees C, or under low water-flow conditions. These effects were reversed by increases in temperature or the applied osmotic gradient. We conclude that apical membrane retrieval causes the phenomenon of flux inhibition.
Risk and Patterns of Secondary Complications in Surgical Inpatients
Authors: Elliot Wakeam, Joseph A. Hyder, Wei Jiang, Stuart A. Lipsitz, Sam Finlayson
Journal: JAMA Surgery (2014)

Little empirical evidence exists on how a first (index) complication influences the risk of specific subsequent secondary complications. Understanding these risks is important to elucidate clinical pathways of failure to rescue or death after postoperative complication.To understand patterns of secondary complications in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP).Matched analysis using a cohort of 890 604 patients undergoing elective inpatient surgery from January 1, 2005, through December 31, 2011, identified in the NSQIP Participant Use Data File. Five index complications were studied: pneumonia, acute myocardial infarction, deep space surgical site infection, bleeding or transfusion event, and acute renal failure. Each patient with an index complication was matched to a control patient based on propensity for the index event and the number of event-free days. Outcomes were compared using conditional logistic regression.Rates of 30-day secondary complications and 30-day mortality.Five cohorts were developed, each with 1:1 matching to controls, which were well balanced. Index pneumonia (n = 7947) was associated with increased odds of 30-day reintubation (odds ratio [OR], 17.1; 95% CI, 13.8-21.3; P < .001), ventilatory failure (OR, 15.9; 95% CI, 12.8-19.8; P < .001), sepsis (OR, 7.3; 95% CI, 6.2-8.6; P < .001), and shock (OR, 13.0; 95% CI, 10.4-16.2; P < .001). Index acute myocardial infarction was associated with increased rates of secondary bleeding or transfusion events (OR, 4.3; 95% CI, 3.3-5.8; P < .001), pneumonia (OR, 5.1; 95% CI, 2.6-10.2; P < .001), cardiac arrest (OR, 12.0; 95% CI, 7.5-19.2; P < .001), and reintubation (OR, 11.7; 95% CI, 8.4-16.3; P < .001). Deep space surgical site infection was associated with dehiscence (OR, 30.4; 95% CI, 19.9-46.5; P < .001), sepsis (OR, 13.1; 95% CI, 10.2-16.7; P < .001), shock (OR, 10.6; 95% CI, 6.4-17.7; P < .001), kidney injury (OR, 8.6; 95% CI, 3.9-18.8; P < .001), and acute renal failure (OR, 10.5; 95% CI, 3.8-29.3; P < .001). Index acute renal failure was associated with increased odds of cardiac arrest (OR, 25.3; 95% CI, 9.3-68.6; P < .001), reintubation (OR, 11.3; 95% CI, 7.4-17.1; P < .001), ventilatory failure (OR, 12.4; 95% CI, 8.2-18.8; P < .001), bleeding or transfusion events (OR, 11.3; 95% CI, 6.3-20.5; P < .001), and shock (OR, 11.2; 95% CI, 7.2-17.3; P < .001).This investigation quantified the effect of index complications on patient risk of specific secondary complications. The defined pathways merit investigation as unique targets for quality improvement and benchmarking.
Buthalitone Sodium in Out-patient Anaesthesia
Authors: A. G. Henderson, J. Mackett
Journal: BMJ (1957)

gated over a period of 18 months.With 25 mg. of dipipanone given by the deep subcutaneous or intra- muscular route, adequate relief of pain in labour was achieved in over 90 % of cases.Dipipanone was found to be a satisfactory adjunct to general anaesthesia.The dose initially required varied from 2.5 to 5 mg.accord- ing to the patient's age, weight, and physical condition.The total dose required for an operation of average duration was from 5 to 10 mg.An alternative technique for the maintenance of con- trolled respiration during thoracotomy is presented, using dipipanone in place of muscle relaxants.We wish to thank Mr. Kirwan Taylor for permission to con- duct the trial of dipipanone in his maternity unit and to Sister Styles and her staff for their co-operation and help.We should also like to express our appreciation of the help we received from Sister Mathias, the senior theatre sister.We owe a special debt to Dr. G.
A Modest Policy Proposal
Authors: Ralph Crawshaw
Journal: JAMA (1984)

EARLY on a raw February morning, I discovered how close this year of 1984 has come to fulfilling George Orwell's prophecy. A bright colleague, thought by some to be a loudmouth, by others a renegade, opened my sleepy eyes to strange possibilities when he sat down beside me at breakfast exclaiming, "I've got it all worked out. To hell with HMOs and PPOs; it is NHSD, the National Health Selective Disservice all the way!" It was 6:45 AM and we were at the counter of the Central Cafe, a hole-in-the-wall beanery, a block and a half from the local hospital. It's the kind of place that tries to live down its honest working man's heritage of red plastic upholstered chrome-plated stools and formica counter top by piping in classical music and labeling hash-brown potatoes "cottage fries" on the menu. My friend, or more precisely, my acquaintance, was still in his
LICHEN PLANUS HYPERTROPHICUS.
Authors: DAVID LIEBERTHAL
Journal: JAMA (1902)

There are a number of names for this affection: Lichen simplex chronicus circumscriptus; lichen verrucosus, lichen corneus, etc., most of which are appropriate to this morbid process. In the last two decades it has been the subject of lively discussion, inasmuch as some cases of this description do not yield to the administration of arsenic, others do not show any typical lichen papules, but only the verrucous patches are characteristic of this disease and hence there arises serious doubt whether in these cases we have really to deal with a true lichen-planus process or with an atypical form of mycosis fungoides—A. Neiser, Deutscher Dermatologen Congress, 1894—or with a lichenization of a localized pruritus in the sense of Brocq. Thus further, Kaposi has named cases of this appearance keratosis verrucosa papillaris. Now, this question as to the identity of these with lichen planus has lately been answered in the affirmative, after
Points: Awards for research into crippling diseases
Authors: J. Walford
Journal: BMJ (1986)

ever, urine osmolality depends-not only on secretion of antidiuretic hormone but also on the kidney's ability to respond.If the kidney's concentratmg ability haa been lost the urine will.bedilute irrespective of the level ofantidiuretic hormone, so the finding ofa dilute urne in this situation does not by itself permit any conclusion to be drawn about antidiuretic hormone secretion.Furthermore, if the kidney is insensitive.toantidiuretic hormone urine osmoLality conveys .noinformation on the setting of the osmostat, which can be assessed only by direct assay of antidiuretic hormoneas a function of serum osmolality Totally implantable vascular access for long.term chemotherapy Dr M F-McMULUN (Royal Victoria Hospital,eat BTl2 6BA) writes: Following the comments of MrA E Youngandcolleagues (7 tecember,-p 1608) I would like to draw attention to another advantage of.thePort-a-Cath.In this unit two patients have used the Hickdman -catheter as a means of attempted suicide, Both patients, young men, had Hickman catheters inserted for intensive chemotherapy, and both attempted suicide by-removing large quantities of blood through the catheter.Despite the problems of assessment, psychiarc disorders are.common among patients with cancer, 2 and cancercan increase the risk of suicide.3In both these patiepis the Hickman catheter,,which.the patients mpulated daily tb selves, was an easy means of access tao the circulatin.Perhaps the insertion of.a Port-a-Cath would have ayoided this complication.
Cinaciguat, a soluble guanylate cyclase activator: results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes
Authors: Mihai Gheorghiade, Stephen J. Greene, Gerasimos Filippatos, Erland Erdmann, Roberto Ferrari, Phillip D. Levy, Aldo Maggioni, Christina Nowack, Alexandre Mebazaa
Journal: European Journal of Heart Failure (2012)
Norepinephrine Controls Astroglial Responsiveness to Local Circuit Activity
Authors: Martin Paukert, Amit Agarwal, Jaepyeong Cha, Van A. Doze, Jin U. Kang, Dwight E. Bergles
Journal: Neuron (2014)

Astrocytes perform crucial supportive functions, including neurotransmitter clearance, ion buffering, and metabolite delivery. They can also influence blood flow and neuronal activity by releasing gliotransmitters in response to intracellular Ca2+ transients. However, little is known about how astrocytes are engaged during different behaviors in vivo. Here we demonstrate that norepinephrine primes astrocytes to detect changes in cortical network activity. We show in mice that locomotion triggers simultaneous activation of astrocyte networks in multiple brain regions. This global stimulation of astrocytes was inhibited by alpha-adrenoceptor antagonists and abolished by depletion of norepinephrine from the brain. Although astrocytes in visual cortex of awake mice were rarely engaged when neurons were activated by light stimulation alone, pairing norepinephrine release with light stimulation markedly enhanced astrocyte Ca2+ signaling. Our findings indicate that norepinephrine shifts the gain of astrocyte networks according to behavioral state, enabling astrocytes to respond to local changes in neuronal activity.
Association of Myocardial T1-Mapping CMR With Hemodynamics and RV Performance in Pulmonary Hypertension
Authors: Ana García-Álvarez, Inés García-Lunar, Daniel Pereda, Rodrigo Fernández-Jimenez, Javier Sánchez-González, Jesús G. Mirelis, Mario Nuño-Ayala, Damian Sánchez-Quintana, Leticia Fernández-Friera, Jose M. García-Ruiz, Gonzalo Pizarro, Jaume Agüero, Paula Campelos, Manuel Castellá, Manel Sabaté, Valentin Fuster, Javier Sanz, Borja Ibañez
Journal: JACC. Cardiovascular imaging (2014)
“Indeterminate” Microvolt T-Wave Alternans Tests Predict High Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction
Authors: Elizabeth S. Kaufman, Daniel M. Bloomfield, Richard C. Steinman, Pearila B. Namerow, Ottorino Costantini, Richard J. Cohen, J. Thomas Bigger
Journal: Journal of the American College of Cardiology (2006)
Dual role of hexadecylphosphocholine (miltefosine) in thermosensitive liposomes: Active ingredient and mediator of drug release
Authors: Lars H. Lindner, Martin Hossann, Michael Vogeser, Nicole Teichert, Kirsten Wachholz, Hansjoerg Eibl, Wolfgang Hiddemann, Rolf D. Issels
Journal: Journal of Controlled Release (2007)
Value and Limitations of Electrocardiogram in Diagnosis of Slight and Subacute Coronary Attacks
Authors: D. Short
Journal: BMJ (1968)

The electrocardiogram recorded at the initial consultation was compared with the final diagnosis in 211 consecutive suspected slight or sub-acute coronary attacks in 206 patients.In 77 (36%) of the 211 episodes, acute (or subacute) myocardial infarction was finally diagnosed. The initial E.C.G. showed a diagnostic pattern in only 19 (25%) of these 77 episodes; in 39 (50%) it was abnormal but not diagnostic of recent infarction; while in 19 (25%) the E.C.G. showed no abnormality classified under the Minnesota Code, though in 16 of these there were definite minor changes.In 61 (29%) of the 211 episodes acute myocardial infarction was excluded and an alternative diagnosis was made. The E.C.G. was strictly normal in only 23 (38%) of these 61 episodes; in 15 (25%) it showed minor abnormalities, and in 23 (38%) it was grossly abnormal.
Targeting the Mitogen-Activated Protein Kinase Pathway: Physiological Feedback and Drug Response
Authors: Christine A. Pratilas, David B. Solit
Journal: Clinical Cancer Research (2010)

Abstract Mitogen-activated protein kinase (MAPK) pathway activation is a frequent event in human cancer and is often the result of activating mutations in the BRAF and RAS oncogenes. Targeted inhibitors of BRAF and its downstream effectors are in various stages of preclinical and clinical development. These agents offer the possibility of greater efficacy and less toxicity than current therapies for tumors driven by oncogenic mutations in the MAPK pathway. Early clinical results with the BRAF-selective inhibitor PLX4032 suggest that this strategy will prove successful in a select group of patients whose tumors are driven by V600E BRAF. Relief of physiologic feedback upon pathway inhibition may, however, attenuate drug response and contribute to the development of acquired resistance. An improved understanding of the adaptive response of cancer cells to MAPK pathway inhibition may thus aid in the identification of those patients most likely to respond to targeted pathway inhibitors and provide a rational basis for tailored combination strategies. Clin Cancer Res; 16(13); 3329–34. ©2010 AACR.
IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice
Authors: Dong Li, Rodrigo Guabiraba, Anne-Gaëlle Besnard, Mousa Komai-Koma, Majid S. Jabir, Li Zhang, Gerard J. Graham, Mariola Kurowska-Stolarska, Foo Y. Liew, Charles McSharry, Damo Xu
Journal: Journal of Allergy and Clinical Immunology (2014)

The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis.We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis.Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)(-/-) C57BL/6 mice treated with the recombinant mature form of IL-33 or anti-IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry.IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti-IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-β1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-β1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo.IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.
Cellular Mechanisms for Insulin Resistance in Normal Pregnancy and Gestational Diabetes
Authors: Linda A. Barbour, Carrie E. McCurdy, Teri L. Hernandez, John P. Kirwan, Patrick M. Catalano, Jacob E. Friedman
Journal: Diabetes Care (2007)

The incidence of gestational diabetes mellitus (GDM) has doubled over the last 6–8 years and is paralleling the obesity epidemic. GDM carries long-term implications for the subsequent development of type 2 diabetes in the mother and increased risk for obesity and glucose intolerance in the offspring. Insulin resistance exists before pregnancy in women with a history of GDM but worsens during gestation. Insulin secretion is inadequate to compensate for the insulin resistance, leading to hyperglycemia that is detected by routine glucose screening in pregnancy. Thus, chronic insulin resistance is a central component of the pathophysiology of GDM.

Human pregnancy is characterized by a series of metabolic changes that promote adipose tissue accretion in early gestation, followed by insulin resistance and facilitated lipolysis in late pregnancy. In early pregnancy, insulin secretion increases, while insulin sensitivity is unchanged, decreased, or may even increase (1,2). However, in late gestation, maternal adipose tissue depots decline, while postprandial free fatty acid (FFA) levels increase and insulin-mediated glucose disposal worsens by 40–60% compared with prepregnancy (2). The ability of insulin to suppress whole-body lipolysis is also reduced during late pregnancy (3), and this is further reduced in GDM subjects (4), contributing to greater postprandial increases in FFAs, increased hepatic glucose production, and severe insulin resistance (2,5–7). Although various placental hormones have been suggested to reprogram maternal physiology to meet fetal needs, the cellular mechanisms for this complex transition remain obscure (8). Further, the critical molecular mechanisms involved in increasing maternal lipid flux in obese women throughout pregnancy that may underlie skeletal muscle insulin resistance and increased fetal fuels are just beginning to be investigated.

Skeletal muscle is the principal site of whole-body glucose disposal, and along with adipose tissue, becomes severely insulin resistant during the latter half of pregnancy. Normal …
Effects of isoproterenol on abnormal intraventricular conduction.
Authors: M S Halpern, P A Chiale, G J Nau, J Przybylski, J O Lázzari, M V Elizari, M B Rosenbaum
Journal: Circulation (1980)

An isoproterenol infusion (1.0-4.0 microgram/min) was administered to 15 patients with intermittent bundle branch block (BBB) and two patients with apparently fixed BBB. Three main effects were documented: (1) In all patients with phase 3, or tachycardia-dependent, BBB, isoproterenol caused a pronounced shortening of refractoriness in the affected fascicle. (2) In patients showing phase 4, or bradycardia-dependent, BBB, isoproterenol prolonged the phase 4 block range, probably because of enhanced diastolic depolarization. In one patient (four studies) in whom phase 4 block was not present, isoproterenol caused the appearance of a phase 4 block range. (3) In the two patients with fixed BBB, isoproterenol restored conduction, probably as a result of a hyperpolarizing effect. This study shows that isoproterenol tends to restore or improve conduction related to tachycardia-dependent block, but may impair conduction related to bradycardia-dependent block.
Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain.
Authors: D N Hart, J W Fabre
Journal: The Journal of Experimental Medicine (1981)

In this study, we have used a mouse monoclonal antibody to rat Ia (RT1-B or class II) antigens to demonstrate, by immunofluorescence on frozen sections, intensely Ia-positive dendritic cells in the interstitial connective tissues of every tissue we have examined (heart, liver, thyroid, pancreas, skin, kidney, ureter, and bladder) with the striking exception of brain. The characteristics of the interstitial dendritic cell found in heart were studied in detail, and this cell was shown to be negative for acid phosphatase, beta-glucuronidase, and ATPase activity, and certainly some and probably all of the cells were negative for nonspecific esterase activity. Experiments with colloidal carbon suggested that the cell was either poorly or not at all phagocytic. The cells were negative for surface immunoglobulin and the W3/13 antigen, but positive for the leukocyte common antigen and the SD (Class I) antigens of the major histocompatibility complex. The cell was shown to be of bone marrow origin, and either the cell itself, or more probably its precursor, was shown to be sensitive to irradiation and to cyclophosphamide. All strains tested--including the nude rat--had large numbers of interstitial dendritic cells. The widespread distribution, except in brain, of this cell, which resembles in every respect the dendritic cell described by Steinman et al. (4) in the spleen and lymph nodes of the mouse, is of interest, and the implications in this finding are discussed.