tbuckley/cabot-search huggingface dataset:
Value of Anion-Gap Determination in Multiple Myeloma
Authors: André De Troyer, Anna Stolarczyk, Diederik Zegers de Beyl, Pierre Stryckmans
Journal: New England Journal of Medicine (1977)

Hyponatremia has frequently been observed in patients with multiple myeloma, in some being associated with a relative hyperchloremia.1 , 2 More recent investigations have shown that, in multiple myeloma, the anion gap is lowered as compared to normal controls,3 4 5 6 thereby confirming that the total anions are not decreased in the same proportion as the total cations. This low anion gap was accounted for by the presence of large amounts of circulating cationic paraproteins.3 However, none of these studies provided extensive documentation on the possible diagnostic value of the anion gap in multiple myeloma, nor did they provide data on the relation between . . .
New Treatment Options for Bartter's Syndrome
Authors: Robert Kleta, Candan Basoglu, Eberhard Kuwertz-Bröking
Journal: New England Journal of Medicine (2000)

To the Editor: Bartter's syndrome is a major cause of congenital salt wasting. As a consequence of abnormal salt reabsorption in the thick ascending limb of Henle's loop due to mutations in the lum...
Circulating Insulin-Like Growth Factor Binding Protein-1 and the Risk of Pancreatic Cancer
Authors: Brian M. Wolpin, Dominique S. Michaud, Edward L. Giovannucci, Eva S. Schernhammer, Meir J. Stampfer, JoAnn E. Manson, Barbara B. Cochrane, Thomas E. Rohan, Jing Ma, Michael N. Pollak, Charles S. Fuchs
Journal: Cancer Research (2007)

Abstract Insulin-like growth factor (IGF)-I has growth-promoting effects on pancreatic cancer cells, and elevated fasting serum insulin has been linked to pancreatic cancer risk. IGF binding protein-1 (IGFBP-1) is a downstream target of insulin and inhibits IGF-I activity. To investigate whether prediagnostic plasma levels of IGFBP-1 are associated with pancreatic cancer risk, we did a prospective, case-control study nested within the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. We assayed circulating IGFBP-1 among 144 pancreatic cancer cases that occurred ≥4 years after plasma collection and in 429 controls, matched for date of birth, prospective cohort, smoking status, and fasting status. When compared with participants in the three highest quartiles of plasma IGFBP-1, those in the lowest quartile experienced a relative risk (RR) for pancreatic cancer of 2.07 [95% confidence intervals (95% CI), 1.26–3.39], after adjusting for other risk factors, including circulating IGF-I, IGF binding protein-3, and C-peptide. Only participants in the lowest quartile of plasma IGFBP-1 showed an elevated risk of pancreatic cancer. The influence of low plasma IGFBP-1 became progressively stronger with time; among cases diagnosed ≥8 years after blood collection, the adjusted RR was 3.47 (95% CI, 1.48–8.14), comparing the bottom versus the top three quartiles. The influence of plasma IGFBP-1 was most marked among participants who never smoked cigarettes (RR, 3.30; 95% CI, 1.48–7.35). Among participants in four U.S. prospective cohort studies, low plasma IGFBP-1 levels significantly predicted an increased risk of pancreatic cancer. [Cancer Res 2007;67(16):7923–8]
Renal failure after cholangiography.
Authors: I. L. Craft, J. D. Swales
Journal: BMJ (1967)

Pregnancy in Young Primigravidae-Utian MEDBRITJISOURNA of pre-eclampsia.Only prompt and active treatment prevented a higher incidence of eclampsia.The single case of eclampsia occurred in a 16-year-old unbooked patient who presented at term with a blood pressure of 200/150 mm.Hg, no significant increase in weight, and no albumin in the urine.It became apparent in the management of these young patients that proteinuria was not a constant feature and its absence should not lull one into a false sense of complacency.Increase in Prematurity Rate.-It has been shown in this study that young primigravidae have an increased tendency to begin spontaneous labour before term.These findings are in marked contrast to those of Clough (1958), who reported on 175 young primigravidae and stated that these patients went beyond the expected date of confinement more often than older primigravidae.Both Bochner (1962) and Stearn (1963) found that the birth weights were much the same as in the control groups.Of more significance was the finding of a corrected prematurity rate of 7% in young primigravidae and of 2% in the controls.Of nine studies included in Table II, a prematurity rate of 10% or greater is demonstrated in five (Aznar and Bennett, 1961 ; Bochner, 1962; Hassan and Falls, 1964; Jarvinen and Katila, 1959; Poliakoff, 1958).This prematurity rate is to some extent reflected in a higher perinatal mortality rate in the younger patients.Increased Frequency of Prolonged Labour.-There is no uniformity of opinion on what constitutes prolonged labour.In the reported studies on young primigravidae the upper limit for labour varies from 24 hours (Poliakoff, 1958 ; Aznar and Bennett, 1961) to 48 hours (Sinclair, 1952).The reported average duration for normal labour varies from 9 hours and 42 minutes to 16 hours and 32 minutes (Clough, 1958 ; Hassan and Falls, 1954).Further analysis of these studies revealed that the first stage, rather than the second stage, was what deter-
After eradication: India's post-polio problem
Authors: N. Bhandari
Journal: BMJ (2014)

<h3>Abstract</h3> Homeostatic and circadian processes play a pivotal role in determining sleep structure, timing and quality. In sharp contrast with the wide accessibility of the EEG index of sleep homeostasis, an electrophysiological measure of the circadian modulation of sleep is still non-available. As a consequence, the circadian component of sleep regulation is assumed, but not assessed in routine polysomnographic records. Available evidence suggests that sleep spindle frequencies are markers of the circadian modulation of sleep. In order to test the above assumption, the Budapest-Munich database of sleep records (N = 251), as well as an afternoon nap sleep record database (N = 112) were analysed by the Individual Adjustment Method of sleep spindle analysis. Slow and fast sleep spindle frequencies were characterized by U-shaped overnight dynamics, with highest values in the first and the fourth-to-fifth sleep cycle and the lowest values in the middle of the sleeping period (cycles 2–3). Age-related attenuation of sleep spindle deceleration was evident. Estimated phases of the nadirs in sleep spindle frequencies were advanced in children as compared to other age groups. Additionally, nap sleep spindles were faster than night sleep spindles (0.57 and 0.39 Hz difference for slow and fast types, respectively). Our findings suggest that the circadian modulation of sleep is measurable by a fine frequency resolution analysis of sleep spindles. Moreover, age-related attenuation of circadian sleep modulation can be measured by assessing the overnight dynamics in sleep spindle frequency. Phase of the minimal sleep spindle frequency is a putative biomarker of chronotype.
Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2−/− mice
Authors: Emina Halilbasic, Romina Fiorotto, Peter Fickert, Hanns‐Ulrich Marschall, Tarek Moustafa, Carlo Spirli, Andrea Fuchsbichler, Judith Gumhold, Dagmar Silbert, Kurt Zatloukal, Cord Langner, Uday Maitra, Helmut Denk, Alan F. Hofmann, Mario Strazzabosco, Michael Trauner
Journal: Hepatology (2009)

24-norursodeoxycholic acid (norUDCA), a side chain-modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases. We aimed to better understand the physiologic and therapeutic properties of norUDCA and to test if they are related to its side chain length and/or relative resistance to amidation. For this purpose, Mdr2(-/-) mice, a model for sclerosing cholangitis, received either a standard diet or a norUDCA-, tauro norursodeoxycholic acid (tauro- norUDCA)-, or di norursodeoxycholic acid (di norUDCA)-enriched diet. Bile composition, serum biochemistry, liver histology, fibrosis, and expression of key detoxification and transport systems were investigated. Direct choleretic effects were addressed in isolated bile duct units. The role of Cftr for norUDCA-induced choleresis was explored in Cftr(-/-) mice. norUDCA had pharmacologic features that were not shared by its derivatives, including the increase in hepatic and serum bile acid levels and a strong stimulation of biliary HCO(3)(-)-output. norUDCA directly stimulated fluid secretion in isolated bile duct units in a HCO(3)(-)-dependent fashion to a higher extent than the other bile acids. Notably, the norUDCA significantly stimulated HCO(3)(-)-output also in Cftr(-/-) mice. In Mdr2(-/-) mice, cholangitis and fibrosis strongly improved with norUDCA, remained unchanged with tauro- norUDCA, and worsened with di norUDCA. Expression of Mrp4, Cyp2b10, and Sult2a1 was increased by norUDCA and di norUDCA, but was unaffected by tauro- norUDCA.The relative resistance of norUDCA to amidation may explain its unique physiologic and pharmacologic properties. These include the ability to undergo cholehepatic shunting and to directly stimulate cholangiocyte secretion, both resulting in a HCO(3)(-)-rich hypercholeresis that protects the liver from cholestatic injury.
Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome
Authors: P Tan, A Wei, S Mithraprabhu, N Cummings, H B Liu, M Perugini, K Reed, S Avery, S Patil, P Walker, P Mollee, A Grigg, R D'Andrea, A Dear, A Spencer
Journal: Blood Cancer Journal (2014)

Abstract Therapeutic options are limited for elderly patients with acute myeloid leukemia (AML). A phase Ib/II study was undertaken to evaluate the maximum-tolerated dose (MTD) and preliminary efficacy of the pan-histone deacetylase inhibitor panobinostat (LBH589) in combination with azacitidine in patients with AML or high-risk myelodysplastic syndrome (MDS) naïve to intensive chemotherapy. Thirty-nine patients (AML=29, MDS=10) received azacitidine 75 mg/m 2 subcutaneously (days 1–5) and oral panobinostat (starting on day 5, thrice weekly for seven doses) in 28-day cycles until toxicity or disease progression. Dose-limiting toxicities during the phase Ib stage were observed in 0/4 patients receiving 10 mg panobinostat, in 1/7 patients (fatigue) receiving 20 mg, in 1/6 patients (fatigue) receiving 30 mg and in 4/5 patients (fatigue, syncope, hyponatremia and somnolence) receiving 40 mg. In phase II, an additional 17 patients received panobinostat at a MTD of 30 mg. The overall response rate (ORR=CR+CRi+PR) in patients with AML was 31% (9/29) and that in patients with MDS was 50% (5/10). After a median follow-up of 13 months, the median overall survival was 8 and 16 months in patients with AML and MDS, respectively. Increased histone H3 and H4 acetylation was a useful early biomarker of clinical response. Combining panobinostat with azacitidine was tolerable and clinically active in high-risk MDS/AML patients, warranting further exploration.
Is This Clinical Trial Fully Registered? — A Statement from the International Committee of Medical Journal Editors
Authors: Catherine D. De Angelis, Jeffrey M. Drazen, Frank A. Frizelle, Charlotte Haug, John Hoey, Richard Horton, Sheldon Kotzin, Christine Laine, Ana Marusic, A. John P.M. Overbeke, Torben V. Schroeder, Harold C. Sox, Martin B. Van Der Weyden
Journal: New England Journal of Medicine (2005)

In September 2004, the members of the International Committee of Medical Journal Editors (ICMJE) published a joint editorial aimed at promoting registration of all clinical trials.1 We stated that we will consider a trial for publication only if it has been registered before the enrollment of the first patient. This policy applies to trials that start recruiting on or after July 1, 2005. Because many ongoing trials were not registered at inception, we will consider for publication ongoing trials that are registered before September 13, 2005. Our goal then and now is to foster a comprehensive, publicly available database of . . .
Family Consent to Orders Not to Resuscitate
Authors: Grant E. Steffen
Journal: JAMA (1991)

To the Editor.—  Two recent articles 1,2 argue that when a physician determines that cardiopulmonary resuscitation (CPR) would be futile, then the physician should be allowed to write the do not resuscitate (DNR) order without permission from the competent patient or the incompetent patient's surrogate. In the first article, Hackler and Hiller addressed the hospital policy that requires this permission and argued that not only when CPR is determined to be futile but also when the physician believes that the burdens of CPR clearly outweigh the benefits, the physician should be allowed to write the DNR order without the surrogate's permission.  I agree with Hackler and Hiller and have argued 3 that treatment goals are legitimate if, among other things, they are empirically possible and ethically justified. In the two cases that Hackler and Hiller describe, the surrogates' treatment goals, presumably successful resuscitation, were not legitimate. In both cases, resuscitation
Accidental Toddler Drowning in 5-Gallon Buckets
Authors: Mary I. Jumbelic
Journal: JAMA (1990)

We have identified a previously unrecognized source of accidental drowning in infants and toddlers: 5-gal (19-L) industrial buckets. Twelve cases of drownings in these large-capacity buckets constituted 24% of all infant and toddler (age &lt;3 years) drownings investigated by the Cook County (Illinois) Medical Examiner's Office from January 1985 to June 1989. The buckets, all with 5-gal and 18-kg capacity, are constructed of heavy, rigid plastic and are intended for industrial use. Home use, typically as mop buckets, was associated with the toddlers' death. The large size and heavy construction of these buckets as well as the toddlers' cephalad center of gravity and undeveloped coordination prohibit the toddlers from extricating themselves after peering into and falling inside the buckets. Parents and public health officials should be advised that domestic use of these containers poses a serious threat to the safety of curious toddlers. Adults should never leave toddlers unattended around even small amounts of water. (<i>JAMA</i>. 1990;263:1952-1953)
Review of Christine Overall,<i>Why Have Children: The Ethical Debate</i>
Authors: Andrea Mechanick Braverman
Journal: The American Journal of Bioethics (2012)

"Review of Christine Overall, Why Have Children: The Ethical Debate ." The American Journal of Bioethics, 12(8), p. 42 Notes 1 Cambridge, MA: MIT Press, 2012, 272 pages. $27.95
Science Reporters Hear Wide Range of Recent Data at 12th Annual Conference
Authors: Andrew A. Skolnick
Journal: JAMA (1993)

THE LATEST developments in fields as diverse as psychiatry for the elderly, gene therapy for children, preventing restenosis after cardiac surgery in the middle-aged, and health care reform for everyone were presented to science reporters who gathered in Philadelphia, Pa, for the American Medical Association's 12th Annual Science Reporters Conference. The event was cosponsored by the University of Pennsylvania Medical Center and supported by an educational grant from Burroughs Wellcome Co, Research Triangle Park, NC. <h3>Preventing Restenosis</h3> Eliot Barnathan, MD, estimates that millions of dollars could be saved by preventing the restenosis of blood vessels that commonly occurs after coronary artery angioplasty and atherectomy. Preventing blockage of coronary artery bypass grafts may result in even greater savings, because fewer patients would require repeat surgery. Barnathan, an assistant professor of medicine at the University of Pennsylvania Medical Center, says he believes that the key to preventing restenosis is controlling smooth muscle
Polymorphism T → C (−34 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study
Authors: Bárbara Echiburú, Francisco Pérez-Bravo, Manuel Maliqueo, Fernando Sánchez, Nicolás Crisosto, Teresa Sir-Petermann
Journal: Metabolism (2008)
Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice
Authors: Alexander H. Licht, Tobias Nübel, Anja Feldner, Nathalie Jurisch-Yaksi, Marco Marcello, Elena Demicheva, Jun-Hao Hu, Bettina Hartenstein, Hellmut G. Augustin, Markus Hecker, Peter Angel, Thomas Korff, Marina Schorpp-Kistner
Journal: Journal of Clinical Investigation (2010)

Cellular contractility and, thus, the ability to alter cell shape are prerequisites for a number of important biological processes such as cytokinesis, movement, differentiation, and substrate adherence. The contractile capacity of vascular smooth muscle cells (VSMCs) is pivotal for the regulation of vascular tone and thus blood pressure and flow. Here, we report that conditional ablation of the transcriptional regulator Junb results in impaired arterial contractility in vivo and in vitro. This was exemplified by resistance of Junb-deficient mice to DOCA-salt-induced volume-dependent hypertension as well as by a decreased contractile capacity of isolated arteries. Detailed analyses of Junb-deficient VSMCs, mouse embryonic fibroblasts, and endothelial cells revealed a general failure in stress fiber formation and impaired cellular motility. Concomitantly, we identified myosin regulatory light chain 9 (Myl9), which is critically involved in actomyosin contractility and stress fiber assembly, as a Junb target. Consistent with these findings, reexpression of either Junb or Myl9 in Junb-deficient cells restored stress fiber formation, cellular motility, and contractile capacity. Our data establish a molecular link between the activator protein-1 transcription factor subunit Junb and actomyosin-based cellular motility as well as cellular and vascular contractility by governing Myl9 transcription.
Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery
Authors: Uptal D. Patel, Amit X. Garg, Harlan M. Krumholz, Michael G. Shlipak, Steven G. Coca, Kyaw Sint, Heather Thiessen-Philbrook, Jay L. Koyner, Madhav Swaminathan, Cary S. Passik, Chirag R. Parikh
Journal: Circulation (2012)

Background— Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery. Methods and Results— The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40–2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06–9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67–0.69; P =0.02) and severe AKI (0.73–0.75; P =0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061–0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067–0.506). Conclusions— Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00774137.
Hongjie Yu: monitoring avian influenza in China
Authors: Mark Honigsbaum
Journal: The Lancet (2009)

To many people the prospect of taking charge of an immunisation programme for an area twice the size of Texas would be daunting, especially when their brief was to eradicate polio—a disease rarely seen today in the west. But when Hongjie Yu was offered the chance, shortly after graduating from China Medical University, in 1994, to join the Center for Disease Control and Prevention in Liaoning he didn't hesitate. Yu was to spend 7 years in Liaoning—a province in northern China with a population of 40 million—during which time he travelled in the province coordinating the delivery of polio and other vaccines to remote towns and villages.
GP league tables are too simple and should not be used, says BMA
Authors: Z. Kmietowicz
Journal: BMJ (2013)

GPs’ performance should not be compared in league tables because these would not properly reflect the quality of care provided, the BMA has said.

The BMA was responding to a consultation launched by NHS England in August on how general practice should develop,1 part of its wider 10 year strategy to transform the NHS.

It said that league tables created from primary care data “generally focus on overly simplistic figures” that would “fail to reflect the complexities of general practice” and should be avoided.2

The NHS regulator, the Care Quality Commission, is currently developing a rating system for primary care.3 Though the BMA has warned the commission of its concerns, it has acknowledged that the ratings could benefit patients. It said that it “would like to work with CQC and NHS England to try …
Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology
Authors: Stefan Baenziger, Mathias Heikenwalder, Pål Johansen, Erika Schlaepfer, Ursula Hofer, Regina C. Miller, Simone Diemand, Kenya Honda, Thomas M. Kundig, Adriano Aguzzi, Roberto F. Speck
Journal: Blood (2008)
PSYCHOSOCIAL MORBIDITY FACTORS MEDIATE THE RELATIONSHIP BETWEEN HEART DISEASE COMPLEXITY AND LOWER QUALITY OF LIFE
Authors: Bradley S. Marino, Amy E. Cassedy, Dennis Drotar, Gil Wernovsky, Rodney Franklin, Kate Brown, David Rosenthal, John Breidert, Melanie Riedel, Anne Kazak, Jo Wray
Journal: Journal of the American College of Cardiology (2012)