tbuckley/cabot-search huggingface dataset:
Evidence for cAMP-Independent Mechanisms Mediating the Effects of Adrenomedullin, a New Inotropic Peptide
Authors: István Szokodi, Pietari Kinnunen, Pasi Tavi, Matti Weckström, Miklós Tóth, Heikki Ruskoaho
Journal: Circulation (1998)

Adrenomedullin (ADM), a new vasorelaxing and natriuretic peptide, may function as an endogenous regulator of cardiac function, because ADM and its binding sites have been found in the heart. We characterize herein the cardiac effects of ADM as well as the underlying signaling pathways in vitro.In isolated perfused, paced rat heart preparation, infusion of ADM at concentrations of 0.1 to 1 nmol/L for 30 minutes induced a dose-dependent, gradual increase in developed tension, whereas proadrenomedullin N-20 (PAMP; 10 to 100 nmol/L), a peptide derived from the same gene as ADM, had no effect. The ADM-induced positive inotropic effect was not altered by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP8-37, or H-89, a cAMP-dependent protein kinase inhibitor. ADM also failed to stimulate ventricular cAMP content of the perfused hearts. Ryanodine (3 nmol/L), a sarcoplasmic reticulum Ca2+ release channel opener, suppressed the overall ADM-induced positive inotropic effect. Pretreatment with thapsigargin (30 nmol/L), which inhibits sarcoplasmic reticulum Ca2+ ATPase and depletes intracellular Ca2+ stores, attenuated the early increase in developed tension produced by ADM. In addition, inhibition of protein kinase C by staurosporine (10 nmol/L) and blockade of L-type Ca2+ channels by diltiazem (1 micromol/L) significantly decreased the sustained phase of ADM-induced increase in developed tension. Superfusion of atrial myocytes with ADM (1 nmol/L) in isolated left atrial preparations resulted in a marked prolongation of action potential duration between 10 and -50 mV transmembrane voltage, consistent with an increase in L-type Ca2+ channel current during the plateau.Our results show that ADM enhances cardiac contractility via cAMP-independent mechanisms including Ca2+ release from intracellular ryanodine- and thapsigargin-sensitive Ca2+ stores, activation of protein kinase C, and Ca2+ influx through L-type Ca2+ channels.
Glycosylated Hemoglobin and Mortality in Patients with Nondiabetic Chronic Kidney Disease
Authors: Vandana Menon, Tom Greene, Arema A. Pereira, Xuelei Wang, Gerald J. Beck, John W. Kusek, Allan J. Collins, Andrew S. Levey, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2005)

In the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA1c) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA1c was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels >126 mg/dl (n = 20), or missing HbA1c levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA1c with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m2. Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA1c was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA1c was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA1c and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA1c is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA1c may be important as a risk stratification tool in this high-risk population.
Assessing clinical trials--simple randomisation.
Authors: S M Gore
Journal: BMJ (1981)

Statistics in QuestionSHEILA M GORE determine a convenient systematic way of reading the table of random numbers.The layout reproduced here makes it sensible to use a column of two-digit numbers-for example, 78, 38, 37-and to read down the column.C'P,IC ~~~~The third step is to select a starting point.Using a pin I chose *50.For illustration only a fragment from a table of random numbers is reproduced here.Do not use this fragment in practice; consult a more extensive table, select one from the several pages of random numbers therein, and choose a starting ~'~~~~' ~~~~~point on that page.These selections need not be made in a strictly random fashion-the use of a pin is not unusual, for EPCXMMWY ~~~~~~~~~~~~~~~~~~~Table of random numbers
Human Relations and Hospital Care
Authors: Marjorie C. Meehan
Journal: JAMA (1965)

Patienthood in the Mental Hospital: An Analysis of Role, Personality, and Social Structure.  By Daniel J. Levinson and Eugene B. Gallagher. 265 pp. $5.95. Houghton Mifflin Co., 2 Park St, Boston, 1964  Although an overwhelming amount has been written about patients, in or out of hospitals, only recently has anyone thought to investigate the patient's attitude toward the hospital. If feelings affect the course of an illness, the patient's reaction to the hospital is significant for his health. Recently two studies have been directed toward the investigation of this problem.  Cartwright, a sociologist, conducted a survey in which over 700 patients recently discharged from hospitals in England and Wales were interviewed. In Human Relations and Hospital Care , she presents her findings. On the whole, patients seemed reasonably satisfied, but there were many complaints, especially about delays in admission, lack of privacy, and difficulty in obtaining information about their illness and
The Distribution of Neurokinin-1 and Neurokinin-2 Receptors in Human Central Airways
Authors: CRISTINA E. MAPP, DEBORAH MIOTTO, FAUSTO BRACCIONI, MARINA SAETTA, GRAZIELLA TURATO, PIERO MAESTRELLI, JAMES E. KRAUSE, VLADIMIR KARPITSKIY, NORMAN BOYD, PIERO GEPPETTI, LEONARDO M. FABBRI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The precise locations of neurokinin (NK)-1 and NK-2 receptors in human airways, and their role in airway inflammatory diseases, have not been carefully examined. To determine the distribution of NK-1 and NK-2 receptors in human central airways, and to determine whether their distribution was different in smokers, we examined surgical specimens from patients undergoing lung resection for limited lung lesions. We mapped NK-1 and NK-2 receptors in four groups of subjects: four asymptomatic nonsmokers, seven asymptomatic smokers, seven symptomatic smokers with normal lung function, and eight symptomatic smokers with chronic airflow limitation. Tissues were immunostained with anti-NK-1- and anti-NK-2-receptor antibodies. Expression of NK-1 and NK-2 receptors was quantified through light microscopy and image analysis. Both NK-1 and NK-2 receptors were found in bronchial glands, bronchial vessels, and bronchial smooth muscle. Although no receptors were observed in the epithelium, receptors were occasionally found in nerves (NK-1) and in inflammatory cells (NK-2) such as T lymphocytes, macrophages, and mast cells. The distribution of both NK-1 and NK-2 receptors was similar in all the tissues examined in the four groups of subjects. These data show that NK-1 and NK-2 receptors are present in human central airways and that their expression is not modified by cigarette smoking.
Conference calls for one NHS complaints procedure
Authors: D. Carnall, L. Beecham, a. J. Smith
Journal: BMJ (1995)

The meeting supported unanimously a motion from the Leeds Division opposing the government's proposal that NHS trusts should be able to set up independent complaints procedures and calling for one NHS procedure. The chairman of CCSC's negotiating subcommittee, Dr Caroline Marriott, told the conference, “The potential for over 400 …
The Demise of the Physical Exam
Authors: Sandeep Jauhar
Journal: New England Journal of Medicine (2006)

One afternoon, at the beginning of my first clinical clerkship in internal medicine, my team was called to the intensive care unit. A patient, whom I'll call Mr. Abbott, had just been admitted with excruciating chest pain that had started a few hours earlier. He was in his early 50s, extensively tattooed, just the sort of tough I wouldn't want to meet alone in a parking lot at night — but right then he was whimpering. He kept stroking his sternum up and down, as if trying to rub the pain away. It was obvious that he was having an . . .
Allogeneic bone marrow transplantation and donor lymphocyte infusion in a mouse model of irradiation-induced myelodysplastic/myeloproliferation syndrome (MD/MPS): evidence for a graft-versus-MD/MPS effect
Authors: B Sprangers, B Van Wijmeersch, A Luyckx, X Sagaert, L De Somer, O Rutgeerts, C Lenaerts, W Landuyt, N Boeckx, B Dubois, C De Wolf-Peeters, M Waer, A D Billiau
Journal: Leukemia (2008)
Influence of Small Atmospheric Ions on the Airways in Patients with Bronchial Asthma
Authors: Ole ØSterballe, Bent Weeke, Ole Albrechsten
Journal: Allergy (1979)

The influence of artificially generated atmospheric ions is studied in 15 patients with bronchial asthma. A slight but significant (at 5% level) improvement in the lung function was demonstrated in nine patients during positive as well as negative ion exposure, but the patients’ subjective votings of the air quality did not show any changes due to ion exposure. No change in the histamine threshold of the airways in six patients with bronchial asthma was demonstrated during exposure to ions. Further controlled studies with electro‐aerosols are needed.
Palestine: the assault on health and other war crimes
Authors: Yoram Blachar
Journal: BMJ (2005)

Editor—I write with regard to Summerfield's much debated article.1 Many of the things that he cites, besides resonating with hatred, are presented in a complete vacuum, and we were surprised to see them published in a respectable medical journal despite the author's clear political agenda and the total lack of corroboration of any claim made.

Israel is required to defend its citizens daily from terrorist activity, an obligation that in no way contradicts the reality in which Israel, on a daily basis, provides medical care to Palestinians.

According to a report of the health coordinator of the civil administration for the West Bank, in the first half of 2004 alone, more than 200 Palestinian children received treatment in Israeli hospitals, and more than 19 000 patients were given permits to receive medical care in Israel. The civil administration also clarified 1000 delays of patients and medical personnel at roadblocks. These are only some examples, taken from the complete report, of the efforts made to ensure health services.

Not only was the care offered, 14 072 751 Israeli shekels (about $3 127 278) worth of debts of the Palestinian Authority to Israeli hospitals were offset.

The conclusion that can be drawn is that Summerfield's article is certainly a one sided view of the situation and totally disregards the context and history of the conflict.

With regard to Summerfield's obsessive and repeated attacks on the Israel Medical Association (IMA) and the World Medical Association (WMA): the IMA has been far from silent in the face of alleged health violations but rather has consistently forwarded such allegations to the army or the government to investigate and deal with. In more than one case, the allegations have proved untrue; in some cases, remedial action was taken; and in several cases, the army defended its actions.

We have met and continue to meet various Israeli, Palestinian, and international representatives to see how the situation might be improved. We have also trained medical officers in the ethical complexities of such a volatile situation, where their kindness and ethical stand might be abused. However, neither the IMA nor the WMA is willing to take a political stand on an issue, or to give credence to the half truths and untruths expressed by Summerfield.
HCO3(-)-dependent intracellular pH regulation in the premature myocardium.
Authors: T Nakanishi, H Gu, M Seguchi, E J Cragoe, K Momma
Journal: Circulation Research (1992)

This study investigated developmental changes in Na(+)-H+ exchange and HCO3(-)-Cl- exchange activities in newborn and adult rabbit hearts. pHi was measured using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in isolated myocytes. Myocardial mechanical function was measured in the isolated ventricular preparation. Intracellular acidosis with normal pHo was induced by an NH4Cl (10 mM) prepulse technique. Upon removal of NH4Cl, pHi fell transiently and then recovered toward the control level. In the HCO3-/CO2-buffered solution, the rate of recovery of pHi in the newborn was greater than in the adult. In the HCO3-/CO2-buffered solution, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of Na(+)-H+ exchange, inhibited the recovery of pHi completely in the adult. In the newborn, however, significant recovery of pHi was observed in the presence of EIPA. In the presence of both EIPA and 4-acetamido-4'-isothiocyanatostilbene-2',2'-disulfonic acid (SITS), an inhibitor of HCO3(-)-Cl- exchange, the recovery of pHi was not observed in the two age groups. In the HEPES-buffered solution that did not contain HCO3-/CO2, the rate of recovery of pHi after NH4Cl removal was similar in the two age groups. In the HEPES-buffered solution, the recovery of pHi was completely inhibited by EIPA in the two age groups. In the presence of EIPA in the HCO3-/CO2-buffered solution, contractile function decreased during acidosis after NH4Cl removal and did not recover in the adult. In the newborn, significant recovery of contractile function was observed after NH4Cl removal in the presence of EIPA. The recovery of mechanical function observed in the presence of EIPA in the newborn was inhibited by SITS. These data suggest that, although there is no developmental change in the Na(+)-H+ exchange activity, HCO3(-)-Cl- exchange is more active in the premature myocardium. The presence of the HCO3(-)-Cl- exchanger is important in maintaining myocardial contractile function during acidosis, especially when Na(+)-H+ exchange is inhibited and may partly explain the greater resistance of the premature myocardium to acidosis.
ABC of Medical Computing: ILLUSTRATING AND PRESENTING YOUR DATA
Authors: N. Lee
Journal: BMJ (1995)

Good quality slides, overheads, and handouts are essential when giving a presentation whether it is a seminar, lecture, or paper at a scientific meeting. They provide a reassuring framework for your talk, help maintain the audience's interest, and make sure the salient points are remembered.

Displaying your key points is a powerful way of focusing the mind of the audience. Text slides or overheads are one of the most useful types of illustrations to create and form the basis of most presentations. The most basic method for making them is to use a word processor attached to an inkjet or laser printer which can print on to acetate sheets for overhead projection or on to paper for the photographic department to make into a slide. Laser quality thermal acetates can be put through most printers or photocopiers.

The more advanced word processors allow considerable embellishment to the presentation. And if you have a colour printer, it is just as easy to produce colour overheads—even on the night before the presentation.

### Text Slide

Simple text slide created with a word processor.

Liquid crystal display (LCD) colour panels link directly to the computer, allowing the computer image to be projected on to a large screen. This avoids the need for acetate sheets. Most presentation packages include a slide show facility, which allows your slides to be displayed one after the other. Producing the presentation is cheap, but the cost of the additional equipment is high. The system is therefore more appropriate for permanent lecture facilities.





Creating 35 mm slides is as easy as making overhead sheets but often requires a little more time to make up the …
Ethical imperative to publish extends to academics too
Authors: D. F Horrobin
Journal: BMJ (1995)

EDITOR,—I support John Pearn's view that publication of research findings is an ethical imperative.1 The medical community at large can assess the status of something only if all the relevant information is available.

The pharmaceutical industry is often accused of selective publication of results, and there is some truth in the accusation. There is just as much truth, however, in the charge that academics also fail to publish important items of information. They may not be driven by financial conflicts …
A Life-Threatening Coronary-Artery Stenosis
Authors: C M Boltwood, T Spitze
Journal: New England Journal of Medicine (2000)

Figure 1. A 74-year-old man presented with a one-week history of exertional angina and dizziness. Treadmill testing showed deep, prolonged depression of the ST segment and hypotension at a low level of exercise. During urgent cardiac catheterization, the 6-French diagnostic catheter recorded severe pressure damping during cannulation of the ostium of the left coronary artery. A single anteroposterior angiogram was quickly obtained before the catheter was removed. The angiogram showed severe stenosis of the left main coronary artery (arrow) and a total absence of contrast reflux despite forceful injection by hand. Since the left coronary artery was dominant and provided . . .
Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations
Authors: B Gerby, E Clappier, F Armstrong, C Deswarte, J Calvo, S Poglio, J Soulier, N Boissel, T Leblanc, A Baruchel, J Landman-Parker, P H Roméo, P Ballerini, F Pflumio
Journal: Leukemia (2011)
Pharmacological targeting of long QT mutant sodium channels.
Authors: D W Wang, K Yazawa, N Makita, A L George, P B Bennett
Journal: Journal of Clinical Investigation (1997)

The congenital long QT syndrome (LQTS) is an inherited disorder characterized by a delay in cardiac cellular repolarization leading to cardiac arrhythmias and sudden death often in young people. One form of the disease (LQT3) involves mutations in the voltage-gated cardiac sodium channel. The potential for targeted suppression of the LQT defect was explored by heterologous expression of mutant channels in cultured human cells. Kinetic and steady state analysis revealed an enhanced apparent affinity for the predominantly charged, primary amine compound, mexiletine. The affinity of the mutant channels in the inactivated state was similar to the wild type (WT) channels (IC50 approximately 15-20 microM), but the late-opening channels were inhibited at significantly lower concentrations (IC50 = 2-3 microM) causing a preferential suppression of the late openings. The targeting of the defective behavior of the mutant channels has important implications for therapeutic intervention in this disease. The results provide insights for the selective suppression of the mutant phenotype by very low concentrations of drug and indicate that mexiletine equally suppresses the defect in all three known LQT3 mutants.
The Riddle of Kawasaki Disease
Authors: Jane C. Burns
Journal: New England Journal of Medicine (2007)

Two generations of clinicians and researchers have been stumped by the riddle of Kawasaki disease. How can an illness look like an infectious disease but not have a recoverable agent; look like an immune-mediated vasculitis but not be easily treated with corticosteroids; and look like a benign, self-limited illness but be the leading cause of acquired heart disease in children? The answers to the riddle continue to elude us.Kawasaki disease affects children of all ethnic backgrounds throughout the world, although susceptibility is shaped by genetic influences. Japanese children have the highest incidence of the disease, with an attack rate . . .
Scalp Hemorrhage as an Emergency in the Newborn
Authors: Philip J. Kozinn
Journal: JAMA (1965)

MASSIVE hemorrhage into the scalp of newborn infants due to various blood dyscrasias has recently been presented as a life-threatening syndrome.<sup>1</sup>The acute loss of more than half of the infant's total blood volume in this manner may necessitate immediate transfusion. The reabsorption of a large hematoma may in turn cause hyperbilirubinemia, which may be severe enough to require an exchange transfusion. Since our earlier report,<sup>1</sup>we have encountered two additional newborn infants with massive bleeding into the scalp secondary to a blood dyscrasia. Our purpose in presenting these added cases is to heighten awareness of this urgent syndrome which can best be recognized by thorough coagulation studies. Postpartum swellings of the scalp of the newborn are usually differentiated into caput succedaneum and cephalhematoma. The former swelling is present at birth, rapidly disappears, and is predominantly edema. The latter may not appear for hours or days after delivery
Characteristics of Uninsured Low-Income Adults in States Expanding vs Not Expanding Medicaid
Authors: Sandra L. Decker, Genevieve M. Kenney, Sharon K. Long
Journal: JAMA Internal Medicine (2014)

Karin V. Rhodes, MD, MS; Genevieve M. Kenney, PhD; Ari B. Friedman, MS; Brendan Saloner, PhD; Charlotte C. Lawson, BA; David Chearo, MA; Douglas Wissoker, PhD; Daniel Polsky, PhD
Failure of buspirone to manage benzodiazepine withdrawal
Authors: Edward Schweizer, Karl Rickels
Journal: American Journal of Psychiatry (1986)

Fifteen patients with 146 cumulative years of tranquilizer use were withdrawn from their benzodiazepine (nine gradually and six abruptly), and buspirone, a new nonbenzodiazepine anxiolytic, was substituted. The addition of buspirone did not appear to lessen the intensity of the withdrawal state. This finding supports preclinical studies indicating that buspirone has no clinically significant benzodiazepine receptor activity.
Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models
Authors: Silvestre Vicent, Ron Chen, Leanne C. Sayles, Chenwei Lin, Randal G. Walker, Anna K. Gillespie, Aravind Subramanian, Gregory Hinkle, Xiaoping Yang, Sakina Saif, David E. Root, Vicki Huff, William C. Hahn, E. Alejandro Sweet-Cordero
Journal: Journal of Clinical Investigation (2010)

KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic KRAS can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers. Using a combination of functional genomics and mouse genetics, we identified a role for the transcription factor Wilms tumor 1 (WT1) as a critical regulator of senescence and proliferation downstream of oncogenic KRAS signaling. Deletion or suppression of Wt1 led to senescence of mouse primary cells expressing physiological levels of oncogenic Kras but had no effect on wild-type cells, and Wt1 loss decreased tumor burden in a mouse model of Kras-driven lung cancer. In human lung cancer cell lines dependent on oncogenic KRAS, WT1 loss decreased proliferation and induced senescence. Furthermore, WT1 inactivation defined a gene expression signature that was prognostic of survival only in lung cancer patients exhibiting evidence of oncogenic KRAS activation. These findings reveal an unexpected role for WT1 as a key regulator of the genetic network of oncogenic KRAS and provide important insight into the mechanisms that regulate proliferation or senescence in response to oncogenic signals.