tbuckley/cabot-search huggingface dataset:
Low-Level Mercury Can Enhance Procoagulant Activity of Erythrocytes: A New Contributing Factor for Mercury-Related Thrombotic Disease
Authors: Kyung-Min Lim, Sujin Kim, Ji-Yoon Noh, Keunyoung Kim, Won-Hee Jang, Ok-Nam Bae, Seung-Min Chung, Jin-Ho Chung
Journal: Environmental Health Perspectives (2010)

BackgroundAssociations between cardiovascular diseases and mercury have been frequently described, but underlying mechanisms are poorly understood.ObjectivesWe investigate the procoagulant activation of erythrocytes, an important contributor to thrombosis, by low-level mercury to explore the roles of erythrocytes in mercury-related cardiovascular diseases.MethodsWe used freshly isolated human erythrocytes and ex vivo and in vivo thrombosis models in rats to investigate mercury-induced procoagulant activity.ResultsProlonged exposure to low-dose mercuric ion (Hg2+; 0.25–5 μM for 1–48 hr) induced erythrocyte shape changes from discocytes to echinocytes to spherocytes, accompanied by microvesicle (MV) generation. These MVs and remnant erythrocytes expressed phosphatidylserine (PS), an important mediator of procoagulant activation. Hg2+ inhibited flippase, an enzyme that recovers PS into the inner leaflet of the cell membrane, and activated scramblase, an enzyme that alters lipid asymmetry in the cell membrane. Consistent with these activity changes, Hg2+ increased intracellular calcium and depleted ATP and protein thiol. A thiol supplement reversed Hg2+-induced MV generation and PS exposure and inhibited the increase in calcium ion (Ca2+) and depletion of ATP, indicating that free-thiol depletion was critical to Hg2+-mediated procoagulant activity. The procoagulant activity of Hg2+-treated erythrocytes was demonstrated by increased thrombin generation and endothelial cell adhesion. We further confirmed Hg2+-mediated procoagulant activation of erythrocytes in ex vivo and in vivo rat thrombosis models, where Hg2+ treatment (0.5–2.5 mg/kg) increased PS exposure and thrombus formation significantly.ConclusionThis study demonstrated that mercury could provoke procoagulant activity in erythrocytes through protein-thiol depletion–mediated PS exposure and MV generation, ultimately leading to enhanced thrombosis.
A History of Electrocardiography
Authors: Dickinson W. Richards
Journal: JAMA (1964)

This is a valuable and interesting compendium of information about the electrocardiogram, its development from earliest beginnings to the present day, and the many physiologists and clinicians who achieved this development. The story is well told, in the simple, nontechnical manner which has characterized so much of the senior author's teaching style. While a large amount of mathematics might have been included, the authors have avoided all but elementary arithmetic. After an introductory chapter the text begins with an account of the development of recording apparatus, from the earliest experiments of Galvani, through the capillary electrometer to the string galvanometer and other modern instruments. There follows a chapter of biographies, the first of which is a delightful sketch of the life and work of the central figure, Willem Einthoven. All the other biographies are extremely short: it would have been interesting, and also appropriate, to have had fuller accounts of
Effect of Doxazosin Gastrointestinal Therapeutic System as Third-Line Antihypertensive Therapy on Blood Pressure and Lipids in the Anglo-Scandinavian Cardiac Outcomes Trial
Authors: Neil Chapman, Choon Lan Chang, Björn Dahlöf, Peter S. Sever, Hans Wedel, Neil R. Poulter
Journal: Circulation (2008)

Background— The role of doxazosin in treatment of hypertension remains controversial. Methods and Results— We evaluated the effects on blood pressure (BP) and biochemical parameters of doxazosin GITS (gastrointestinal therapeutic system) as a third-line antihypertensive agent among 10 069 participants in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm (ASCOT-BPLA) whose BP remained above 140/90 mm Hg (130/80 mm Hg in those with diabetes mellitus). Among those who received doxazosin, mean age was 63 years (SD 9 years), 79% were male, and 32% had diabetes. Doxazosin was initiated a median of 8 months (interquartile range 3 to 24 months) after randomization and was added to a mean of 2.0 (SD 0.3) other antihypertensive drugs; the mean starting and final doses were 4.1 (SD 0.6) and 7.0 (SD 3.1) mg, respectively. During a median of 12 months (interquartile range 4 to 31 months) of uninterrupted doxazosin treatment, during which other antihypertensive treatments remained unchanged, mean BP fell 11.7/6.9 mm Hg (SD 18.8/9.6 mm Hg, P &lt;0.0001) from 158.7/89.2 mm Hg (SD 18.3/10.6 mm Hg). After the addition of doxazosin, 29.7% of participants achieved target BP. There was no apparent excess of heart failure among doxazosin users. There were associated modest favorable effects on plasma lipid profiles, but a small rise in fasting plasma glucose was observed. Doxazosin was generally well tolerated, with 7.5% of participants discontinuing the drug because of adverse events, most frequently dizziness, fatigue, headache, and edema. Conclusions— α-Blockers are no longer recommended as add-on therapy in some hypertension guidelines. However, although they are nonrandomized and were not placebo-controlled, the present findings suggest that doxazosin is a safe and effective third-line antihypertensive agent.
Intestinal adaptation to diabetes. Altered Na-dependent nutrient absorption in streptozocin-treated chronically diabetic rats.
Authors: R N Fedorak, E B Chang, J L Madara, M Field
Journal: Journal of Clinical Investigation (1987)

To examine the pattern and mechanisms of enhanced intestinal nutrient absorption in diabetes, we measured intestinal transport of 3-O-methylglucose (3OMG), l-alanine (ALA), and SO4 in male Lewis rats made diabetic with streptozocin. Diabetes enhanced 3OMG absorption fivefold in ileum and threefold in jejunum; ALA absorption increased twofold in ileum but not at all in jejunum; ileal SO4 transport was unaffected. Increases in 3OMG and ALA transport were due solely to increases in maximum velocity. The enhancement of ileal glucose absorption was half-maximal in 40-45 d, could be reversed by 10 d of treatment with insulin and did not result from adrenergic denervation. The density of glucose carriers per milligram brush border protein (measured as [3H]phlorizin binding sites) was not altered but there was a sixfold increase in the number of glucose-inhibitable [3H]phlorizin-binding sites in the intact epithelium. Generalized mucosal hypertrophy accounted for less than 30% of this increase. We conclude that the intestine adapts to streptozocin-induced diabetes through recruitment of additional brush border carriers for sugar, probably in the midvillus-to-crypt region.
Reading Disability; Progress and Research Needs in Dyslexia
Authors: George E. Park
Journal: JAMA (1962)

This book is the report of a symposium on dyslexia with a postconference review supplement. The symposium, which convened at the Johns Hopkins Medical Institutions last year, had participants well qualified to speak for their respective disciplines. They were concerned, among other factors, with dyslexia as a neurologically based phenomenon, perceptual difficulty, and dysfunction of the interpretive integration. The symposium was deliberately organized at the level of basic research rather than clinical orientation. This procedure has naturally limited, to a degree, the usefulness of the book to those who are generally concerned with research on dyslexia. It is of considerable importance to be aware of the different and confusing senses in which the concept of dyslexia is employed by the various participants; to mention a few: specific dyslexia, congenital dyslexia, congenital word-blindness, and strephosymbolia. Also, there are more questions as to the validity of claims than there is agreement of
Hypertrabeculation vs Left Ventricular Noncompaction on Echocardiogram
Authors: David C. Peritz, Aaron Vaughn, Mario Ciocca, Eugene H. Chung
Journal: JAMA Internal Medicine (2014)

Left ventricular noncompaction (LVNC) is a rare cause of progressive cardiomyopathy thought to result from incomplete myocardial development. It has been associated with an increased risk of sudden death, especially in those with a depressed left ventricular ejection fraction. Thus, the current recommendation for patients with this diagnosis is restriction from participation in competitive sports.An asymptomatic 18-year-old African American collegiate football player had a murmur on his preparticipation physical examination. Subsequent cardiology workup revealed hypertrabeculation vs LVNC. Second and third opinions were sought from national experts in the field: one gave the diagnosis of LVNC and recommended restriction; the other gave the diagnosis of hypertrabeculation. After a family meeting including the player, mother, team physician, and consulting cardiologist, the player was permitted to participate in football.Distinguishing between pathologic LVNC and physiologic hypertrabeculation is a diagnostic challenge and is becoming increasingly commonplace with enhanced echocardiography and magnetic resonance imaging modalities. Given the limited data on such patients, careful workup and discussion between patient and providers is required.
Influence of neutron irradiation on holmium acetylacetonate loaded poly(l-lactic acid) microspheres
Authors: J.F.W Nijsen, A.D van het Schip, M.J van Steenbergen, S.W Zielhuis, L.M.J Kroon-Batenburg, M van de Weert, P.P van Rijk, W.E Hennink
Journal: Biomaterials (2002)
Vitamin A Intoxication
Authors: Gertrud C. Reyersbach, Joseph Hanelin, Robert J. Joplin
Journal: New England Journal of Medicine (1952)

FOR many years it has been known that excessive intake of vitamin A would produce toxic effects in small animals, but not until Joseph's1 report in 1944 was this symptom complex recognized in man. Other reports of poisoning have appeared subsequently,2 3 4 5 6 7 8 9 10 11 12 and Caffey13 has summarized the available data on vitamin A intoxication in human beings. To date, 21 cases have been reported. Because the majority of these publications have appeared in either pediatric or roentgenologic journals, practitioners in general may be unaware of this condition, which is readily curable. Its diagnosis should not be difficult, since it exhibits distinctive clinical . . .
Conference on the Care of Patients With Severe Chronic Pain in Terminal Illness
Authors: Edward N. Brandt
Journal: JAMA (1984)

Millions of Americans with arthritis, back disorders, coronary disease, traumatic injury, and other chronic conditions wage a daily war against pain. In many instances, the pain is severe enough to cause partial or total disability and prevent participation in routine activities. While most patients with severe pain are, in fact, being treated adequately with a wide range of effective analgesics, there continue to be deficiencies in current pain therapy created by voids in our knowledge about pain and its mechanisms as well as by the inadequate or improper application of available knowledge. This situation is particularly true for the terminally ill patient. The impact that pain can have on the patient's life can range from tolerable discomfort to crippling defeat. In spite of great advances in biomedical knowledge and technology, there remain problems with the development, dissemination, and application of knowledge, as well as with misguided attitudes among health professionals.
Tobacco and Graves' Disease
Authors: David S. Cooper
Journal: JAMA (1993)

Graves' disease is an autoimmune disease with a lifetime incidence of 1% to 2% in the general population. Circulating antibodies to the thyrotropin (thyroid-stimulating hormone [TSH]) receptor stimulate growth of the thyroid gland, as well as the synthesis and secretion of excessive amounts of thyroid hormone. These autoantibodies are polyclonal and therefore different clones may have disparate effects on the thyroid gland, possibly by binding and activating different epitopes on the TSH receptor.<sup>1</sup>This variety of effects may be one reason why the size of the thyroid and the amount of hormone secreted are not necessarily correlated. The recent cloning and sequencing of the human TSH receptor should enable detailed study of antibody-receptor interactions.<sup>2</sup>Despite isolation of the causative antibodies, however, there is little known about the processes that trigger the disease in the first place. Current evidence suggests that a defect in T-cell function or number permits
Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development
Authors: John G Meara, Andrew J M Leather, Lars Hagander, Blake C Alkire, Nivaldo Alonso, Emmanuel A Ameh, Stephen W Bickler, Lesong Conteh, Anna J Dare, Justine Davies, Eunice Dérivois Mérisier, Shenaaz El-Halabi, Paul E Farmer, Atul Gawande, Rowan Gillies, Sarah L M Greenberg, Caris E Grimes, Russell L Gruen, Edna Adan Ismail, Thaim Buya Kamara, Chris Lavy, Ganbold Lundeg, Nyengo C Mkandawire, Nakul P Raykar, Johanna N Riesel, Edgar Rodas, John Rose, Nobhojit Roy, Mark G Shrime, Richard Sullivan, Stéphane Verguet, David Watters, Thomas G Weiser, Iain H Wilson, Gavin Yamey, Winnie Yip
Journal: The Lancet (2015)
Preventing the cardiotoxicity of anthracyclines by dexrazoxane
Authors: K Hellmann
Journal: BMJ (1999)

Anthracyclines such as doxorubicin are among the most widely used anticancer drugs and are often given to children as part of curative regimens Yet long term cardiac damage is a major adverse effect that limits the effectiveness of these drugs, particularly in children. The introduction of dexrazoxane to limit the cardiotoxicity of anthracyclines is a real advance in the treatment of some forms of cancer.

Cardiotoxicity induced by anthracyclines primarily affects the myocardium and is dose related, cumulative, and irreversible. Each dose of the anthracycline doxorubicin produces an increment of myocardial damage The normal heart can compensate for this until a lifetime dose of some 450 mg/m2 has been reached, after which the compensatory cardiac mechanisms begin to fail. In childhood malignancies, which may be cured if sufficient anthracyclines can be given, cardiotoxicity is more erratic and severe than in adults.1 Each dose may unpredictably cause severe toxicity, or subclinical cardiotoxicity may become overt only in adolescence or early adulthood.2 A way of preventing cardiotoxicity in children taking anthracyclines will therefore prevent not …
The effect of delayed reperfusion following infarction in the rat on structural changes in viable myocardium
Authors: K McDonald
Journal: Cardiovascular Research (1997)

Objective: Evidence indicates that patency of the infarct related artery following the completion of myocardial necrosis can attenuate ventricular remodeling. Data have also demonstrated that inhibition of infarct expansion contributes to the anti-remodeling effect of delayed reperfusion. However, the influence of a patent artery on components of the remodeling process in the viable myocardium is poorly understood. Methods: Myocyte morphometrics (isolated cell technique) and collagen content (hydroxyproline analysis) were assessed 28 days following experimental myocardial infarction from rats with permanently ligated left coronary vessels (NRP; n = 10) compared with rats who underwent reperfusion 150 minutes after ligation (RP; n = 11) and a sham-operated group (n = 10). Results: Analysis of infarct size (planimetry) in a separate group of rats demonstrated that reperfusion at this late time point did not reduce infarct size (NRP: 33±3 vs. RP: 35±5%). Myocyte length in RP rats was less than in NRP rats in viable, non-infarcted left ventricular tissue (155±3 vs. 167±4 μm, p = 0.02), in the right ventricle (154±4 vs. 167±3 μm, p = 0.02) and in the septum (158±4 vs. 169±4 μm, p = 0.05). Reperfusion also attenuated the expected increase in cell volume compared with NRP rats (left ventricle 39.4±1.7×103 vs. 44.1±1.6×103 μm3, p = 0.06; right ventricle 36.7±1.6×103 vs. 42.7±2.0×103 μm3, p = 0.02; septum 41.0±1.6×103 vs. 44.2±1.8×103 μm3, p = 0.19). Hydroxyproline content increased in the viable left ventricular tissue in both the reperfused and non-reperfused groups. Conclusion: Reperfusion without myocardial salvage attenuates the increase in myocyte length and volume that occurs in remodeling myocardium following infarction in the rat, with no effect on the increase in collagen content. These data indicate that patency of the infarct vessel, which is known to have an inhibitory effect on infarct expansion, also has an anti-remodeling effect remote from the area perfused by this artery.
Use of atropine in patients with acute myocardial infarction and sinus bradycardia.
Authors: M M Scheinman, D Thorburn, J A Abbott
Journal: Circulation (1975)

Fifty-six patients with acute myocardial infarction complicated by sinus bradycardia (SB) were treated with intravenous atropine and monitored in a coronary care unit. Atropine decreased or completely abolished premature ventricular contractions (PVCs) and/or bouts of accelerated idioventricular rhythm in 27 of 31 patients (87%) and brought systemic blood pressure up to normal in 15 of 17 patients (88%) with hypotension. In addition, atropine administration was associated with improved atrioventricular conduction in 11 of 13 patients (85%) with acute inferior myocardial infarction associated with 2 degrees or 3 degrees atrioventricular block. Seven patients developed ten significant adverse effects: ventricular tachycardia or fibrillation in three, sustainedsinus tachycardia in three, increased PVCs in three, and toxic psychosis in one. These major adverse effects correlated with either a higher initial dose of atropine (i.e., 1.0 mg aa compared with the usual 0.5 or 0.6 mg) or a total cumulative dose exceeding 2.5 mg over 21/2 hours. Atropine is the drug of choice for management of patients with SB and hypotension and is effective in the treatment of ventricular arrhythmias as well as conduction disturbances in patients with inferior myocardial infarction. Serious adverse effects, however, preclude use of atropine without careful medical supervision.
Mortality from leukaemia among relatives of patients with cystic fibrosis.
Authors: L. N. al-Jader, R. R. West, M. C. Goodchild, P. S. Harper
Journal: BMJ (1989)

treatment can promote prostatic carcinoma in the elderly.The pathogenesis of hypogonadism in patients with peripheral vascular disease is probably related to atherosclerosis of the testicular and renal arteries and the aorta.We thank Dr N Carr for obtaining the control serum samples and St Thomas's Hospital and Chelsea Hospital for Women for supplying reagents for radioimmunoassay.
Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse
Authors: T Mori
Journal: Cardiovascular Research (2004)

Objective: Previous studies suggest that atrial natriuretic peptide (ANP) may act as an autocrine/paracrine factor to modulate cardiac hypertrophy in response to various stimuli. The effect of ANP deficiency on the response to volume overload has not previously been studied. We hypothesised that ANP deficient mice would develop excess cardiac hypertrophy in response to volume overload stress. Methods: Male homozygous ANP deficient (Nppa−/−) and wildtype (Nppa+/+) male mice maintained on either a normal salt (0.55% NaCl) or low salt (0.05% NaCl) diet from weaning were studied after 2 weeks of volume overload from an aorto-caval fistula (ACF). Unoperated littermates served as controls. Left ventricular (LV) structure and function was evaluated by echocardiography. Heart, LV, and lung weights were determined at sacrifice. Myocyte diameter was measured by morphometric analysis of fixed sections of the left ventricle. Results: BP, heart weight, and LV weight were increased in Nppa−/− vs. Nppa+/+ unoperated mice. Nppa−/− mice developed exaggerated heart and LV weight compared to Nppa+/+ mice following ACF. Increased myocyte diameter paralleled increased echo LV wall thickness following ACF in Nppa+/+ but not Nppa−/− mice fed with 0.55% NaCl, indicating that an alternate mechanism contributed to increased wall thickness in Nppa−/− mice. Mid-wall shortening was mildly depressed in the Nppa−/− vs. Nppa+/+ genotype following ACF with fed 0.55% NaCl. A 0.05% NaCl diet from weaning normalized BP, but did not prevent exaggerated cardiac enlargement and LV hypertrophy following ACF in Nppa−/− mice. Conclusions: ANP-deficient mice exhibited an exaggerated increase in heart and LV weight in response to volume overload, which was not prevented by normalization of blood pressure. The findings suggest that ANP is an important physiologic modulator of the cardiac hypertrophy induced by volume overload.
Acute effects of beta blockade and exercise on mood and anxiety.
Authors: A Head, M J Kendall, R Ferner, C Eagles
Journal: British Journal of Sports Medicine (1996)

To measure the previously reported beta blocker induced adverse changes in mood state and anxiety measures, and to determine if prolonged aerobic exercise attenuates such mood modifications.After 4 days of drug treatment with comparable doses of propranolol (40 and 80 mg), metoprolol (50 and 100 mg), or placebo, mood (POMS) and anxiety states (STAI) were assessed in healthy volunteers, before and after 1 h of treadmill walking exercise at 50% maximum oxygen uptake.Compared to placebo, resting "tension", "depression", and "total mood disturbance" were significantly higher on propranolol 80 mg, but all were reduced with exercise. "Fatigue" and "confusion" were also higher on propranolol, and were unaffected by exercise. "Fatigue" was also higher than placebo after exercise on metoprolol 100 mg. "Anxiety" was unaffected by drug treatment or exercise.The evidence that beta blockers, and particularly propranolol, have adverse effects on mood was confirmed. It would be preferable to prescribe a beta blocker which does not adversely alter mood states. However, exercise significantly reduced the measures of "tension" and "depression" which were adversely increased by propranolol. Exercise prescription may therefore not only be compatible with beta blockade, but a highly desirable adjuvant therapy.
HAZARDS OF DRY CLEANING
Authors: H. S. Cumming
Journal: JAMA (1934)

<h3>To the Editor:—</h3> I have just read the interesting editorial inThe Journal, Dec. 16, 1933, on the hazards of dry cleaning. My attention was called to the statement in the last part of the third paragraph on page 1970 to the effect that "the purchase of gasoline at a filling station may also involve a hazard other than fire—that of tetra-ethyl lead poisoning." Based on a study carried on by the Public Health Service, regulations for the protection of the public were prepared by a committee of scientists appointed by myself with Dr. W. H. Howell as chairman. You are no doubt well acquainted with this committee and its work. I would, however, call your attention to Bulletin 163 from the Public Health Service, "The Use of Tetra-Ethyl Lead Gasoline in Its Relation to Public Health," which gives these regulations. You will note that the committee recommends, among other