tbuckley/cabot-search huggingface dataset:
Dobutamine increases cardiac output of the total artificial heart. Implications for vascular contribution of inotropic agents to augmented ventricular function.
Authors: P F Binkley, K D Murray, K M Watson, P D Myerowitz, C V Leier
Journal: Circulation (1991)

BACKGROUND The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha- and beta-adrenergic agonist activity. METHODS AND RESULTS To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p less than 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p less than 0.005) with dobutamine administration. CONCLUSIONS These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility.
Molecular characterization of an autoantigen of PM-Scl in the polymyositis/scleroderma overlap syndrome: a unique and complete human cDNA encoding an apparent 75-kD acidic protein of the nucleolar complex.
Authors: F Alderuccio, E K Chan, E M Tan
Journal: The Journal of Experimental Medicine (1991)

About 50% of patients with the polymyositis/scleroderma (PM-Scl) overlap syndrome are reported to have autoantibodies to a nuclear/nucleolar particle termed PM-Scl. The particle is composed of several polypeptides of which two have been identified as autoantigens. In this report, human cDNA clone coding for the entire 75-kD autoantigen of the PM-Scl particle (PM-Scl 75) was isolated from a MOLT-4 lambda gt-11 library. The deduced amino acid sequence of the cDNA clone represented a protein of 355 amino acids and 39.2 kD; the in vitro translation product of this cDNA migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at approximately 70 kD. The aberrant migration of the polypeptide in SDS-PAGE was shown to be related to the COOH half that was rich in acidic residues. Authenticity of the cDNA coding for PM-Scl 75 was shown by immunoreactivity of PM-Scl sera with in vitro translation products and recombinant fusion proteins encoded by the cDNA. In addition, rabbit antibodies raised to recombinant fusion protein reacted in immunofluorescence, immunoblotting, and immunoprecipitation with the characteristic features displayed by human anti-PM-Scl sera.
Providing High-Value, Cost-Conscious Care
Authors: Brian Pollak
Journal: Annals of Internal Medicine (2011)

Letters20 December 2011Providing High-Value, Cost-Conscious CareBrian Pollak, MDBrian Pollak, MDFrom Wellspan, York, PA 17403.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-12-201112200-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The Accreditation Council for Graduate Medical Education's system-based practice competency, discussed in Weinberger's article (1), is more than teaching quality improvement and being a team player. “... Residents must be able to utilize resources within the system to provide excellent patient care by ... demonstrating cost effective resource allocation and prescribing patterns that uphold quality ...” (2).References1. Weinberger SE. Providing high-value, cost-conscious care: a critical seventh general competency for physicians. Ann Intern Med. 2011;155:386-8. [PMID: 21930856] LinkGoogle Scholar2. Accreditation Council for Graduate Medical Education. Systems-based Practice: Key Components. Accessed at www.acgme.org/outcome/e-learn/introduction/SBP.html on 22 September 2011. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Wellspan, York, PA 17403.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoProviding High-Value, Cost-Conscious Care: A Critical Seventh General Competency for Physicians Steven E. Weinberger Providing High-Value, Cost-Conscious Care Jeremy D. Graham , Darryl K. Potyk , and Elise D. Raimi Providing High-Value, Cost-Conscious Care Christine K. Cassel Providing High-Value, Cost-Conscious Care Carlos O. Weiss , Maia Holden , and Matthew McNabney Providing High-Value, Cost-Conscious Care Ira S. Nash Providing High-Value, Cost-Conscious Care Christopher L. Knight Providing High-Value, Cost-Conscious Care Erik A. Wallace Providing High-Value, Cost-Conscious Care Steven E. Weinberger Metrics 20 December 2011Volume 155, Issue 12Page: 857KeywordsConflicts of interestGraduate medical educationPatientsQuality improvement ePublished: 20 December 2011 Issue Published: 20 December 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Sepsis: definition, epidemiology, and diagnosis
Authors: Andrew Lever, Iain Mackenzie
Journal: BMJ (2007)

Although tuberculous disease of bones and joints is becoming uncommon, it still occurs and may cause devastating sequelae. It is frequently not diagnosed prior to the onset of permanent damage to the joints or spine; the most important reason for this delay may be the fact that it is not considered in the differential diagnosis of monoarthritis or back pain. Most persons with the disease have other evidence of tuberculosis. Not infrequently an aggressive approach (including synovial biopsy or surgical exploration of the back) is needed to confirm the diagnosis when there are no other clues.
Blocking Vascular Endothelial Growth Factor-A Inhibits the Growth of Pituitary Adenomas and Lowers Serum Prolactin Level in a Mouse Model of Multiple Endocrine Neoplasia Type 1
Authors: Nina Korsisaari, Jed Ross, Xiumin Wu, Marcin Kowanetz, Navneet Pal, Linda Hall, Jeffrey Eastham-Anderson, William F. Forrest, Nicholas Van Bruggen, Franklin V. Peale, Napoleone Ferrara
Journal: Clinical Cancer Research (2008)

Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the combined occurrence of multiple tumors, typically of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland. A mouse model with a heterozygous deletion of the Men1 gene recapitulates the tumorigenesis of MEN1. We wished to determine the role of vascular endothelial growth factor (VEGF)-A in the vascularization and growth of MEN1-associated tumors, with an emphasis on pituitary adenomas.To investigate whether tumor growth in Men1(+/-) mice is mediated by VEGF-A dependent angiogenesis, we carried out a monotherapy with the anti-VEGF-A monoclonal antibody (mAb) G6-31. We evaluated tumor growth by magnetic resonance imaging and assessed vascular density in tissue sections. We also measured hormone levels in the serum.During the treatment with mAb G6-31, a significant inhibition of the pituitary adenoma growth was observed, leading to an increased mean tumor doubling-free survival compared with mice treated with a control antibody. Similarly, the growth of s.c. pituitary adenoma transplants was effectively inhibited by administration of anti-VEGF-A mAb. Serum prolactin was lowered by mAb G6-31 treatment but not by control antibody, potentially providing a new therapeutic approach for treating the hormonal excess in MEN1 patients. Additionally, the vascular density in pancreatic islet tumors was significantly reduced by the treatment.These results suggest that VEGF-A blockade may represent a nonsurgical treatment for benign tumors of the endocrine system.
Approaches to the Mind: Movement of the Psychiatric Schools From Sects Toward Science
Authors: Marjorie C. Meehan
Journal: JAMA (1973)

All psychiatrists agree that their purpose is to help people who are mentally or emotionally disturbed. But that is about all they agree on. Are the people they treat suffering from a disease, reacting to a social situation, or merely playing a role? Should they be treated physically, intellectually, or emotionally? Should the psychiatrist try to make a definite diagnosis, attempt to understand the development of the patient's problem, or offer symptomatic treatment? Many authors have attempted to compare the various schools of thought and to bring about a synthesis or at least to find some common ground. Leston Havens compares several schools and pleads for a pluralistic approach. Havens identified four major schools. The objective-descriptive school, introduced by Kraepelin, utilizes careful examination and history taking, regards the patients as suffering from a definite disease that it is the doctor's duty to identify and treat. The behavior therapists, lobotomists, practitioners
Tenure is justifiable
Authors: W. Bentley MacLeod
Journal: Behavioral and Brain Sciences (2006)

The target article by Ceci et al. provides some interesting results regarding how faculty might react to difficult social dilemmas, but it has little to say about tenure and its effect upon academic freedom. This comment discusses briefly what we know about tenure, and employment protection more generally, and why it may be in a university's best interest to hire tenured faculty. The comment concludes by pointing out that the results make a rather useful contribution regarding the difficulty of eliciting information on malfeasance in organizations, an area of enormous importance. For example, the results may help us understand why the government has introduced rewards for the reporting of fraud under the whistle-blowing provisions of the Federal Claims Act.
Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension
Authors: J.-M. Launay, P. Hervé, K. Peoc'h, C. Tournois, J. Callebert, C.G. Nebigil, N. Etienne, L. Drouet, M. Humbert, G. Simonneau, L. Maroteaux
Journal: Nature Medicine (2002)
Glucose metabolism during leg exercise in man
Authors: John Wahren, Philip Felig, Gunvor Ahlborg, Lennart Jorfeldt
Journal: Journal of Clinical Investigation (1971)

Arterial concentrations and net substrate exchange across the leg and splanchnic vascular bed were determined for glucose, lactate, pyruvate, and glycerol in healthy postabsorptive subjects at rest and during 40 min of exercise on a bicycle ergometer at work intensities of 400, 800, and 1200 kg-m/min. Rising arterial glucose levels and small decreases in plasma insulin concentrations were found during heavy exercise. Significant arterial-femoral venous differences for glucose were demonstrated both at rest and during exercise, their magnitude increasing with work intensity as well as duration of the exercise performed. Estimated glucose uptake by the leg increased 7-fold after 40 min of light exercise and 10- to 20-fold at moderate to heavy exercise. Blood glucose uptake could at this time account for 28-37% of total substrate oxidation by leg muscle and 75-89% of the estimated carbohydrate oxidation. Splanchnic glucose production increased progressively during exercise reaching levels 3 to 5-fold above resting values at the heavy work loads. Close agreement was observed between estimates of total glucose turnover during exercise based on leg glucose uptake and splanchnic glucose production. Hepatic gluconeogenesis-estimated from splanchnic removal of lactate, pyruvate, glycerol, and glycogenic amino acids-could supply a maximum of 25% of the resting hepatic glucose production but could account for only 6-11% of splanchnic glucose production after 40 min of moderate to heavy exercise. IT IS CONCLUDED THAT: (a) blood glucose becomes an increasingly important substrate for muscle oxidation during prolonged exercise of this type: (b) peripheral glucose utilization increases in exercise despite a reduction in circulating insulin levels: (c) increased hepatic output of glucose, primarily by means of augmented glycogenolysis, contributes to blood glucose homeostasis in exercise and provides an important source of substrate for exercising muscle.
Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast growth factor.
Authors: H Kawaguchi, C C Pilbeam, G Gronowicz, C Abreu, B S Fletcher, H R Herschman, L G Raisz, M M Hurley
Journal: Journal of Clinical Investigation (1995)

In serum-free mouse osteoblastic MC3T3-E1 cells, basic fibroblastic growth factor (bFGF) induced mRNA and protein for prostaglandin G/H synthase-2 (PGHS-2), the major enzyme in arachidonic acid (AA) conversion to prostaglandins. mRNA accumulation peaked at 1 h with bFGF 1 nM. In cells stably transfected with a 371-bp PGHS-2 promoter-luciferase reporter, bFGF stimulated luciferase activity, which peaked at 2-3 h with bFGF 1-10 nM. In the presence of exogenous AA, bFGF stimulated PGE2 production, which paralleled luciferase activity. In serum-free neonatal mouse calvarial cultures, bFGF stimulated PGE2 production in the absence of exogenous AA. bFGF stimulated PGHS-2 mRNA accumulation, which peaked at 2-4 h and then decreased; there were later mRNA elevations at 48 and 96 h that were inhibited by indomethacin. In both MC3T3-E1 cells and neonatal calvariae, bFGF produced smaller and slower increases in PGHS-1 mRNA levels than for PGHS-2. bFGF stimulated bone resorption in mouse calvariae with a maximal increase of 80% at 1 nM. Stimulation was partially inhibited by nonsteroidal anti-inflammatory drugs. We conclude that bFGF rapidly stimulates PGE2 production in osteoblasts, largely through transcriptional regulation of PGHS-2, and that prostaglandins mediate some of bFGF's effects on bone resorption.
When necessity becomes opportunity
Authors: F. Godlee
Journal: BMJ (2009)

President Obama’s healthcare reforms continue their slow passage through stormy waters. Will the open letter to Congress signed by 400 prominent doctors and academics give him sufficient boost to push them through (doi:10.1136/bmj.b3865)? Unlikely, I think, but we can always hope. Lack of health insurance is taking a huge toll on America’s health, according to researchers at Harvard University, who found an excess 45 000 deaths a year among uninsured adults even after adjusting for socioeconomic confounders (doi:10.1136/bmj.b3838).

The letter calls for urgent reform to prevent America’s current healthcare crisis turning into a catastrophe. Its recommendations echo Obama’s plan. But there are people at …
Responses of the Superficial Limb Veins of the Dog to Changes in Temperature
Authors: MICHAEL M. WEBB-PEPLOE, JOHN T. SHEPHERD
Journal: Circulation Research (1968)

The lateral saphenous vein of the dog was perfused with homologous blood at constant, flow. Changes in perfusion pressure were used to measure active changes in venous tone. Cooling of the perfusate caused the vein to constrict and warming to relax. Most of the change occurred over the temperature range of 27° to 42°C. The powerful venoconstrictor response to cooling depended on intact sympathetic nerves, since it was reduced by lumbar sympathectomy and largely abolished by alpha-receptor or ganglionic blockade. The response was confined to the vein being cooled. By comparison, cooling the body core when the temperature of the blood in the vein was 37°C caused a generalized constriction of the superficial limb veins. These responses were impaired by anesthetic agents (for example, pentobarbital), by generalized hypoxia, and by arterial hypotension. The data indicate a role for the cutaneous veins in temperature regulation. In the cold, the venous return is directed preferentially to the venae comitantes for heat preservation through countercurrent exchange with the arteries, and in warmth to the superficial veins for heat dissipation.
Proteasome inhibitors increase missense mutated dysferlin in patients with muscular dystrophy
Authors: Bilal A. Azakir, Beat Erne, Sabrina Di Fulvio, Guido Stirnimann, Michael Sinnreich
Journal: Science Translational Medicine (2014)

Proteasome inhibitors increase missense mutated dysferlin expression in skeletal muscle and monocytes in patients with muscular dystrophy.
Biochemical Response of Late Rickets and Osteomalacia to a Chupatty-free Diet
Authors: J. A. Ford, E. M. Colhoun, W. B. McIntosh, M. G. Dunnigan
Journal: BMJ (1972)

Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread.
Knotted Nasogastric Tubing
Authors: Paul D. Larsen
Journal: JAMA (1977)

To the Editor.—  In a recent letter (237:1432, 1977), Morris reported an unusual complication of nasogastric intubation: knotting of the tube within the stomach with resultant traumatic withdrawal through the nose.  While an intern, I discovered a patient's Miller-Abbott tube could not be withdrawn even through the esophagogastric junction because of a large and complex knot. After prolonged and painful manipulation under fluoroscopy, surgical consultation seemed necessary when a radiology consultant and I devised a successful technique to unknot the tube: the stomach was filled with water just to the point of discomfort, and the knot was allowed to float freely within the dilated organ. Within minutes the knot untied itself and the tube was easily withdrawn.  Several years later by chance I came on a frustrated radiologist unsuccessfully attempting to untie a plain nasogastric tube knotted within a patient's stomach. We distended the stomach with water, and once again,
Abstract 4232: Tumor-associated macrophages are responsible for EGF-R triggered upregulation of the Sox-2 signaling pathway in CSCs, which enhance tumorigenicity and tumor metastasis
Authors: Rong Xiang, Debbie Liao, Mei Ting Chen, Tsung-Hsien Chuang, Ralph A. Reisfeld, Yun Ping Luo
Journal: Cancer Research (2010)

Abstract The cancer stem cell (CSC) hypothesis has gained significant recognition as the descriptor of tumorigenesis. The Sox-2 signaling pathway has an important role in the maintenance of CSCs. Tumor-associated macrophages (TAMs) play an ambiguous role in this process. Here, we demonstrate that the expression of Sox-2 was up-regulated in CSC of 4T07 breast cancer cells, effects induced and enhanced by co-culture of tumor cells with TAMs. In fact, after co-culture, 4T07 tumor cells develop an increased number of CSCs with up-regulated expression of stem cell specific markers (Scal-1 and ABCG2), as well as partner genes of Sox-2, i. e. Oct-4 and Nanog. Down regulation of Sox-2 effectively blocks the ability of TAMs to maintain the phenotype of CSC among 4T07 cancer cells, and enhances tumor development and its pulmonary metastasis in a syngeneic Balb/c mouse model. Most importantly, in a mechanism study, we found that the Sox-2 up-regulation was induced by EGF-R activation in CSC that was triggered by EGF, Macrophage Conditioned Medium (MCM) or by co-culture with TAMs. These effects can all be blocked by inhibitors of EGF-R. Our results suggest that TAMs in the tumor microenvironment(TME) provide a niche which is critical in the development and maintenance of CSCs in breast carcinoma. This critical effect of TAMs on CSC development was achieved by up-regulation of the Sox-2 signaling pathway in CSC. This, in turn, was induced by marked activation of EGF-R achieved through interactions between CSCs and TAMs. In summary, over expression of Sox-2 in CSC of 4T07 breast cancer cells was enhanced by activation of EGF-R, which was induced by TAMs in TME. This series of events is responsible for maintaining the phenotype of CSCs which enhances tumor development and pulmonary metastasis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4232.
Effect of posture-induced blood volume expansion on systemic and regional hemodynamics in patients with cirrhosis
Authors: Tadashi Iwao, Toyonaga Atsushi, Masahiro Sato, Kazuhiko Oho, Teruhiro Sakai, Chizuru Tayama, Ryohichi Nakano, Kyuichi Tanikawa
Journal: Journal of Hepatology (1997)