tbuckley/cabot-search huggingface dataset:
Role of the Sympathetic Nervous System in the Sinus Node Resistance to High Potassium
Authors: MARIO VASSALLE, JÜRGEN K. GREINEDER, JACKSON H. STUCKEY
Journal: Circulation Research (1973)

The resistance of sinus node automaticity to high potassium (K) levels was studied in anesthetized dogs by perfusing the sinus node artery with oxygenated Tyrode's solution containing different K concentrations. The following results were obtained. (1) Sinus node automaticity persisted at a K concentration of 21.6 m M , although the pacemaker site tended to shift in and out of the node at this concentration. (2) Sinus node dominance at high K concentrations was progressively lost as sympathetic influences were progressively eliminated. (3) Sinus node pacemaker activity was suppressed at a K concentration lower than 21.6 m M when calcium was omitted from the perfusion fluid. (4) The pacemaker site shifted consistently from the sinus node towards the atrioventricular node at high K concentrations after the elimination of sympathetic activity (5) The transient sinus tachycardia caused by high K concentrations persisted after bilateral vagotomy. It is concluded that catecholamines participate in the resistance of the sinus node to K, suggesting that the difference in resistance to high K concentrations between the sinus node and Purkinje fibers may, in part, result from the more abundant innervation of the sinus node.
Response to Letter Regarding Article, “Patent Foramen Ovale Closure by Radiofrequency Thermal Coaptation: First Experience in the Porcine Model and Healing Mechanisms Over Time”
Authors: Hidehiko Hara, Robert A. Van Tassel, Robert S. Schwartz, Thomas K. Jones, Elena Ladich, Renu Virmani, David Auth, Joseph Eichinger, Robert J. Sommer
Journal: Circulation (2008)
Mammography screening has little or no effect on breast cancer deaths, Swedish data indicate
Authors: S. Mayor
Journal: BMJ (2012)

Drug promiscuity (i.e., inhibition of multiple enzymes by a single compound) is increasingly recognized as an important pharmacological consideration in the drug development process. However, systematic studies of functional or physicochemical characteristics that correlate with drug promiscuity are handicapped by the lack of a good way of quantifying promiscuity. In this article, we present a new entropy-based index of drug promiscuity. We apply this index to two high-throughput data sets describing inhibition of cytochrome P450 isoforms by small-molecule drugs and drug candidates, and we demonstrate how drug promiscuity or specificity can be quantified. For these drug-metabolizing enzymes, we find that there is essentially no correlation between a drug9s potency and specificity. We also present an index to quantify the susceptibilities of different enzymes to inhibition by diverse substrates. Finally, we use partial least-squares regression to successfully predict isoform specificity and promiscuity of small molecules, using a set of fingerprint-based descriptors.
Evaluation of the Second Generation of a Bioresorbable Everolimus-Eluting Vascular Scaffold for the Treatment of De Novo Coronary Artery Stenosis
Authors: Patrick W. Serruys, Yoshinobu Onuma, Dariusz Dudek, Pieter C. Smits, Jacques Koolen, Bernard Chevalier, Bernard de Bruyne, Leif Thuesen, Dougal McClean, Robert-Jan van Geuns, Stephan Windecker, Robert Whitbourn, Ian Meredith, Cecile Dorange, Susan Veldhof, Karine Miquel Hebert, Krishnankutty Sudhir, Hector M. Garcia-Garcia, John A. Ormiston
Journal: Journal of the American College of Cardiology (2011)
IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation
Authors: Melanie Antl, Marie-Luise von Brühl, Christina Eiglsperger, Matthias Werner, Ildiko Konrad, Thomas Kocher, Matthias Wilm, Franz Hofmann, Steffen Massberg, Jens Schlossmann
Journal: Blood (2006)
Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance
Authors: E Kis, T Nagy, M Jani, E Molnar, J Janossy, O Ujhellyi, K Nemet, K Heredi-Szabo, P Krajcsi
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Earlier publications have suggested a possible role for the efflux transporter breast cancer resistance protein (BCRP) in acquired resistance to disease-modifying antirheumatic drugs (DMARDs) such as leflunomide and its metabolite A771726 (teriflunomide). However, there is no direct evidence that BCRP interacts with these drugs. <h3>Objectives:</h3> To characterise the interaction between BCRP transporter and leflunomide and its active metabolite A771726, with emphasis on the nature of the interaction (substrate or inhibitor) and the kinetic characterisation of the interactions. <h3>Methods:</h3> Different in vitro membrane-based methods (ATPase and vesicular transport assay) using BCRP-HAM-Sf9 membrane preparations and cellular assays (Hoechst assay and cytotoxicity assay) were performed on PLB985-BCRP and HEK293-BCRP cell lines overexpressing BCRP. <h3>Results:</h3> In all assays used, an interaction between the investigated drugs and BCRP was detected. In the vesicular transport assay, both leflunomide and its metabolite inhibited BCRP-mediated methotrexate transport. Both compounds are likely substrates of BCRP as shown by the vanadate-sensitive ATPase assay. In line with the membrane assays, leflunomide and A771726 inhibited BCRP-mediated Hoechst efflux from PLB985-BCRP cells. In the cytotoxicity assay, overexpression of BCRP conferred 20.6-fold and 7.5-fold resistance to HEK293 cells against leflunomide and A771726, respectively. The resistance could be reversed by Ko134, a specific inhibitor of BCRP. <h3>Conclusion:</h3> Based on these results, BCRP could play an important role in the resistance to leflunomide and A771726 via interactions with these drugs. BCRP may also mediate drug-drug interactions when leflunomide is administered with other BCRP substrate drugs such as methotrexate.
Transient Increase in Interleukin-8 and Pulmonary Microvascular Permeability following Aortic Surgery
Authors: Pieter G. H. M. Raijmakers, A. B. Johan Groeneveld, Jan A. Rauwerda, Anton J. Schneider, G. J. Jaap Teule, C. Erik Hack, Lambertus G. Thijs
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10)and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) × 10−3/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-α1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-α) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05). Ischemia/reperfusion of the lower body associated with aortic surgery probably activates neutrophils through a non-complement- and non-TNF-α-mediated pathway and transiently releases IL-8. This in turn may further activate neutrophils and promote their sequestration in the lungs, thereby resulting in transient changes in the pulmonary microvasculature, involving an increase in permeability and decrease in ACE release. None of the aortic surgery patients developed adult respiratory distress syndrome (ARDS) related to surgery during follow-up in the intensive care unit, although some had transient radiographic evidence of pulmonary edema. Nevertheless, our data may help to explain the development of ARDS after major vascular surgery.
Portal vein embolization as a complication of Histoacryl injection for a bleeding giant gastric ulcer
Authors: C.-S. Fan, M.-S. Soon
Journal: Endoscopy (2007)

A 56-year-old man with schizophrenia presented with acute hematemesis. He had been taking nonsteroidal anti-inflammatory drugs frequently for headache. Emergency panendoscopy revealed a huge gastric ulcer on the posterior wall, high in the body of the stomach. The ulcer had a large visible vessel in its base. The vessel was coated with red clot but there was active oozing under the clot ([Figure 1]).
Hemodynamic effects of intravenous sematilide in patients with congestive heart failure: A class III antiarrhythmic agent without cardiodepressant effects
Authors: Bruce S. Stambler, Stephen S. Gottlieb, Bramah N. Singh, Kodangudi B. Ramanathan, J. David Ogilby, Kenneth A. Ellenbogen
Journal: Journal of the American College of Cardiology (1995)

This study sought to evaluate the hemodynamic effects of intravenous sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction. Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans. In 39 patients with congestive heart failure and a left ventricular ejection fraction <40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen. The study had an 80% power to detect clinically meaningful differences in hemodynamic variables. Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 ± 8% [mean ±SD] and 18 ± 10%, respectively) and corrected QT interval (4 ± 8% and 14 ± 10%), and high dose sematilide decreased heart rate by 7 ± 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction ≤25% or >25% and in patients with cardiac index <2 or ≥2 liters/min per m2. Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose. Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiarrhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses.
Book Review Falling Through the Safety Net: Americans Without Health Insurance By John Geyman. 222 pp. Monroe, Me., Common Courage Press, 2005. $29.95 (cloth); $18.95 (paper). 1-56751-255-0 (cloth); 1-56751-254-2 (paper). Uninsured in America: Life and Death in the Land of Opportunity By Susan Starr Sered and Rushika Fernandopulle. 247 pp. Berkeley, University of California Press, 2005. $24.95. 0-520-24442-7
Authors: Daniel M. Fox
Journal: New England Journal of Medicine (2005)
Contribution of Head-Up Tilt Testing and ATP Testing in Assessing the Mechanisms of Vasovagal Syndrome
Authors: Daniel Flammang, Mark Erickson, Sally McCarville, Timothy Church, Djamel Hamani, Erwan Donal
Journal: Circulation (1999)

Background —In patients with vasovagal syndrome, head-up tilt testing may reproduce symptoms generally associated with vasodepression. Recent research suggests ATP testing identifies patients with abnormal vagal cardiac inhibition. This preliminary study examined the joint contribution of both tests in identifying underlying mechanisms in the general population with vasovagal syndrome. Methods and Results —Both tests were performed in random order during 1 session and outside of predominant sympathetic periods in 72 patients hospitalized for syncope (n=56) or presyncope (n=16) for whom no cardiac or extracardiac cause was found. For passive and isoproterenol-provocative tilt testing by standard protocol, reproduction of symptoms defined a positive test. The ATP test consisted of injecting ATP 20 mg IV at bedside, continuously monitoring ECG and blood pressure; a vagal cardiac pause &gt;10 seconds defined a positive test. For most patients (64%), ≥1 test was positive. Of the 41 patients (57%) with a positive tilt test (either passive or provoked by isoproterenol), 32% had cardiac disease; none had significant bradycardia (&lt;50 bpm). Of the 8 patients (11%) with a positive ATP test, 62% had cardiac disease; the probability of a positive result increased with age ( P =0.015). Both tests were positive in 3 patients and negative in 26 patients; the tilt and ATP test results were uncorrelated ( P =0.28). Conclusions —Results suggest tilt and ATP tests individually and jointly determine the mechanism of vasovagal symptoms in most patients and that vagal cardiac inhibition increases with age.
Cancer and Aging: Why Not Waltz Together?
Authors: J. M. Bennett
Journal: CA A Cancer Journal for Clinicians (2001)

The burden of cancer is felt disproportionately among the elderly with the majority of cancers occurring in adults over the age of 65. Dr. Bennett briefly examines the implications of this fact, and acknowledges the growing evidence that clinicians are ill equipped to handle the complex management issues of their elderly patients. CA will continue this series on geriatric oncology in future issues.
Fatal Papillary Necrosis in a Kidney Graft
Authors: Samir Tuma
Journal: JAMA (1976)

RENAL papillary necrosis has been reported as complicating pyelonephritis and diabetes,<sup>1</sup>ureteral obstruction,<sup>2</sup>and other ischemic processes.<sup>3-5</sup>Although it has been associated with kidney transplant,<sup>6,7</sup>it has not, to the best of our knowledge, caused primary acute failure of a kidney graft. We describe such a case. <h3>Report of a Case</h3> A 14-year-old girl with terminal renal failure owing to medullary cystic disease was admitted to our hospital for long-term hemodialysis in 1967. Fasting and postprandial blood glucose levels were repeatedly within normal range. A year later, in January 1968, a cadaveric kidney transplantation was performed. The warm and cold ischemic times were 55 and 140 minutes respectively. The graft failed to function, although the donor's other kidney had been successfully transplanted to another recipient, and long-term satisfactory renal function has been achieved. Angiograms made 18 days after the transplantation showed patent arterial anastomosis of the
STUDIES ON PHOTO-OXIDATION OF ANTIGEN AND ANTIBODIES
Authors: Hans Smetana, David Shemin
Journal: The Journal of Experimental Medicine (1941)

1. Quantitative precipitin studies indicate that progressive photo-oxidation progressively destroys the antigenic function of egg albumin. 2. Quantitative precipitin reactions of antisera (anti-egg albumin rabbit serum and antipneumococcus Type I horse serum) demonstrate that progressive photo-oxidation causes progressive lowering of the potency of the sera. 3. Quantitative precipitin reactions of the photo-oxidized globulin gamma fraction of anti-egg albumin rabbit serum and of Felton solution of antipneumococcus Type I horse serum show that these specific antibody fractions behave similarly to antibodies in whole sera. 4. Egg albumin whose precipitin reaction is destroyed by photo-oxidation no longer causes anaphylaxis in guinea pigs and does not produce precipitins in rabbits. 5. Chemical studies of progressively photo-oxidized egg albumin show a progressive destruction of tryptophane and histidine while tyrosine remains intact and cystine is reversibly oxidized. Sulfhydryl groups can no longer be demonstrated in photo-oxidized egg albumin whose antigenic characteristics are greatly weakened. 6. Similar studies on the globulin gamma fraction of anti-egg albumin rabbit serum and on Felton solution show no diminution of these amino acids in photo-oxidized material whose antigenic properties are destroyed. 7. The non-coagulable nitrogen and the amino nitrogen of egg albumin, antisera, and their specific antibody fractions show but an insignificant increase during photo-oxidation, indicating that the loss of the precipitin reaction is not due to splitting of the respective protein molecules. 8. Electrophoretic studies of egg albumin, antisera, and their specific antibody fractions show that photo-oxidation causes a marked alteration of the pattern of these substrates. 9. Photo-oxidation of proteins causes the formation of aggregates, indicating denaturation. 10. Hematoporphyrin migrates with the albumin fraction of unaltered as well as the photo-oxidized anti-egg albumin rabbit serum and pneumococcus Type I horse serum; in isolated proteins such as egg albumin, globulin gamma, or Felton solution, etc., the dye moves independently of the protein; after progressive photo-oxidation Hp becomes progressively fixed to the protein. Eosin behaves similarly to hematoporphyrin.
Treatment of acute abscesses in the casualty department.
Authors: M H Simms, F Curran, R A Johnson, J Oates, J C Givel, R Chabloz, J ALexander-Williams
Journal: BMJ (1982)

In the treatment of acute pyogenic soft-tissue abscess incision, curettage, and primary suture was compared with incision and drainage alone in a randomised prospective trial. Operations were performed under antibiotic cover by casualty officers, and patients were reviewed by an independent observer in a septic dressing clinic. Altogether 114 patients were studied, of whom 54 were treated by curettage and primary suture and 60 by simple drainage. The mean healing time was 8.9 days in those treated by primary suture and 7.8 days in those treated by simple drainage (p less than 0.05). Primary healing failed to occur in 19 (35%) of the sutured wounds, but there were no other complications in either group. It is concluded that incision and drainage alone is adequate treatment for acute soft-tissue abscess.
METHOD OF OBTAINING THE BEST POSSIBLE ASEPTIC CONDITION DURING OPERATIONS DONE AT PLACES OTHER THAN HOSPITALS.
Authors: J. F. REGER
Journal: JAMA (1896)

Pregnant with glory as are the annals of surgery from its earliest history to the middle of the nineteenth century, illuminated as it has been through the darkness of its endless struggles by the wisdom of such men as Hippocrates, Harvey, Jenner and the two Hunters in the old world, and Physic, Mott, Morton and Gross of the new, it was left to the closing years of this century to furnish such a revolution in surgery as was never dreamed of by its most brilliant and ambitious votaries, as it was thought and taught by the most eminent authorities that ulcerating stumps, sloughing flaps, and discharging sinuses, excessive rises in temperature, gangrene, etc., were due entirely to vicious conditions of the system, humors, imperfect ventilation and poisons that were inhaled; when cleanliness was urged it was as much for cosmetic reasons as any other. When Sir Joseph Lister startled the
Treatment of So-called Palindromic Rheumatism with Gold Compounds
Authors: E. W. Boland, N. E. Headley
Journal: Annals of the Rheumatic Diseases (1949)

A relatively rare form of arthritis was described by Hench andRosenberg in 1941 and in 1944.The syndrome is characterized by frequently recurring attacks of pain, swelling, redness, and disability involving usually one joint at a time, but sometimes multiple joints.The attacks last for short periods and then subside completely without leaving -joint residue.They considered it to be a " new disease ", an entity separate from rheumatoid arthritis and distinguishable clinically from other forms of recurring acute arthritis.To this syndrome the name " palindromic rheumatism " was applied.From an analysis of their thirty-four cases, Hench and Rosenberg outlined the clinical characteristics of palindromic rheumatism.In summary, these were as follows: (1) multiple afebrile attacks of acute arthritis characterized by pain, swelling, tendemess, varying degrees of redness, and increased local heat; (2) frequent recurrences (88 per cent. of cases averaging twenty-three attacks per year) at irregular intervals (few hours to two weeks in most cases); (3) attacks of short duration (80 per cent.lasting a few hours to three days); (4) attacks usually affecting a single joint (90 per cent. of cases);(5) disability often considerable with temporary loss of function of the involved part; (6) complete restitution of joint appearance and function follow- ing attacks; (7) para-arthritis, consisting of red tender swellings near a joint (30 per cent. of cases), and frequent involvement of finger pads; (8) absence of general constitutional signs and symptoms;
SHALL THE PUBLIC TAKE FULL RESPONSIBILITY FOR SMALLPOX?
Authors: W. V. Gage
Journal: JAMA (1924)

To the Editor:  —While attending a meeting of the Northwestern Medical Association, held at Lovell, Wyo., September 4, I was impressed so fully by a remark made by Dr. Evard Olson, secretary of the society, relative to the handling of the vaccination question, that I feel called on to ask for a modest amount of space inThe Journal, that Dr. Olson's idea may receive the publicity it deserves.  Dr. Olson stated that the nonquarantining of all smallpox cases would soon result in the universal adoption of vaccination. Vaccination either is, or is not, a fallacy. If vaccination is efficient, quarantine is unnecessary. Dr. Olson argued that if all smallpox cases were unquarantined, and that if all citizens were given to understand that such conditions existed, and also that the positive protection against the disease, i. e., vaccination, was offered, and that whosoever will, may come, that the matter of