tbuckley/cabot-search huggingface dataset:
Mechanical and neuroendocrine regulation of the endocrine heart
Authors: A. J. de Bold, B. G. Bruneau, M. L. Kuroski de Bold
Journal: Cardiovascular Research (1996)

The cardiac natriuretic peptides (NP) -- atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) -- are polypeptide hormones produced by cardiocytes in the atria of mammals. ANF and BNP are continuously released from the heart, but appropriate mechanical or neuroendocrine stimuli increase their rate of release with or without a concomitant increase in synthesis. The results of our investigations lead us to propose that the endocrine response of the heart to pressure or volume load varies in relation to whether the challenge is acute, subacute or chronic. The acute response to stretch is based on a phenomenon referred to as "stretch-secretion coupling" which results in enhanced secretion of NP stored in the atria. NP release following stretch is made at the expense of a depletable NP pool with no apparent effect on synthesis. The stimulation of NP production that is seen during mineralcorticoid escape is referred to as "subacute" and is characterized by stimulation of atrial ANF and BNP gene transcription secondary to volume overload in which plasma ANF, but not plasma BNP, is significantly elevated. With chronic stimulation, as seen in DOCA-salt treatment at the hypertensive stage, activation of the cardiac fetal program in ventricle is seen together with a stimulation of ANF and BNP production in both atria and ventricles. However, the activation of NP gene expression in the atria is not necessarily associated with fetal isogene expression even though the ventricular hypertrophic process is characterized by the expression of fetal isogenes, including ANF and BNP, that are normally expressed in the fetal ventricle. It seems likely that the acute stimulation of NP release is based on an electromechanical coupling. However, protracted stimulation of release is seen in situations in which profound neuroendocrine changes have taken place, thus suggesting that the primary stimulus for chronically enhanced NP gene expression and NP release is based on changes in the hormonal environment of the atrial cardiocyte. It is concluded that the endocrine heart responds to changes in hemodynamic load with specific changes in translational, post-translational and storage processes for ANF and BNP following acute or chronic stimulation. As a result, plasma levels of ANF and BNP may be used as indicators of the degree of atrial hemodynamic overload and ventricular hypertrophy, respectively. It may be advanced that the endocrine heart differentiates and responds to different hemodynamic challenges in either acute or chronic conditions with specific changes in transcription, translation, post-translational processing, storage, and release of ANF and BNP. We propose that this differentiation is part of the reason for the heart to produce two hormones with similar spectra of activity. This paradigm warrants further investigation.
Lowered B-Type Natriuretic Peptide in Response to Levosimendan or Dobutamine Treatment Is Associated With Improved Survival in Patients With Severe Acutely Decompensated Heart Failure
Authors: Alain Cohen-Solal, Damien Logeart, Bidan Huang, Danlin Cai, Markku S. Nieminen, Alexandre Mebazaa
Journal: Journal of the American College of Cardiology (2009)
Drugs as causative agents and therapeutic agents in inflammatory bowel disease
Authors: Phani Krishna Kondamudi, Rajkumar Malayandi, Chandramohan Eaga, Deepika Aggarwal
Journal: Acta Pharmaceutica Sinica B (2013)

Ulcerative colitis and Crohn's disease are collectively known as inflammatory bowel diseases (IBD) which are chronic inflammatory disorders of gastrointestinal tract. The etiopathogenesis of IBD has been extensively studied but not fully revealed. Recent advances in physiology, molecular biology and pharmacology have provided some insight into the basic etiopathogenetic causes such as genetic, immunologic, etc. This review focuses on drugs involved in the cause of the disease and the investigational new drugs, current therapeutic strategies and their clinical benefits.
Points from Letters: Disposable Syringes
Authors: M. E. Arnold
Journal: BMJ (1966)

that thoughtless minority who are out to claim all they can without concern for their doctor's discomfiture.Rather than embark on propaganda designed to prevent abuse of a tottering ser- vice I look forward to the day when a more positive approach becomes evident-namely, providing the general practitioner with the proper premises and facilities so badly needed to cope adequately with the sort of medicine required of him in this modern age.If distributing leaflets is the best that can be done I hope the planners find other means of so doing rather than through us.-Iam, etc., Resolven, Glam.
The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo
Authors: David M. Lucas, Ryan B. Edwards, Gerard Lozanski, Derek A. West, Jungook D. Shin, Melissa A. Vargo, Melanie E. Davis, Darlene M. Rozewski, Amy J. Johnson, Bao-Ning Su, Virginia M. Goettl, Nyla A. Heerema, Thomas S. Lin, Amy Lehman, Xiaoli Zhang, David Jarjoura, David J. Newman, John C. Byrd, A. Douglas Kinghorn, Michael R. Grever
Journal: Blood (2009)
Effects of chronic digitalization on cardiac and renal Na+ + K+-dependent adenosine triphosphate activity and circulating catecholamines in the dog.
Authors: B R Nechay, R E Jackson, M G Ziegler, S L Neldon, J D Thompson
Journal: Circulation Research (1981)

To extend our understanding of the mechanism of action of digitalis drugs, we studied electrocardiograms (ECGs), renal function, plasma concentrations of catecholamines, and myocardial and renal Na+ + K+-dependent adenosine triphosphate (Na+ + K+ ATPase) activity in chronically digitalized dogs. Five healthy, male, mongrel dogs received a therapeutic regimen of digoxin (0.1 mg/kg on day 1 in three divided doses followed by 0.025 mg/kg per day) orally for 2-4 months. This resulted in plasma digoxin concentrations of 1.1 to 4.7 ng/ml as determined by radioimmunoassay. Six control dogs received daily gelatin capsules by mouth. ECGs monitored throughout the study showed no changes. Digitalized dogs had elevated plasma norepinephrine concentrations (347 vs. 137 pg/ml in controls) and no change in plasma epinephrine concentrations. Digitalized dogs had elevated glomerular filtration rates (0.74 vs. 0.94 ml/min per g of kidney) without significant changes in renal handling of electrolytes and water. All of the above studies were done without the aid of restraining drugs or infusions. The animals were killed with an overdose of pentobarbital for in vitro studies. In digitalized dogs, microsomal Na+ + K+ ATPase-specific activity was 26 to 33% lower in the renal cortex, medulla, and papilla, and 46% lower in the cardiac left ventricle than in control dogs. Digitalization did not alter the osmolalities of renal tissues. We conclude that chronic reduction Na+ + K+ ATPase activity by one-third dose does not cause abnormalities in renal handling of electrolytes and water, and inhibition of Na+ + K+ ATPase in the left ventricular muscle by one-half is associated with no obvious ECG changes in the dog. Further, elevated plasma norepinephrine concentrations may contribute to both the therapeutic and the toxic effects of digitalis.
Between aspiration and reality
Authors: Polly Toynbee
Journal: BMJ (2002)

New guidance for medical schools has recently been issued by the General Medical Council. Polly Toynbee thinks the document has been written to refute the old complaints about arrogant, god-like consultants. She says that if new doctors come out of medical school imbued with the ethos of the guidance then we might expect a new generation of hypersensitive and thoughtful doctors, but she warns that human nature is bound to intervene

What makes the perfect modern doctor? The General Medical Council has drawn up new guidance for medical schools as a framework on which to base their curriculums and assessments. Tomorrow's Doctors (see www.gmc-uk.org/) is an idealistic compendium of the best qualities every new doctor should acquire. If medical schools could indeed turn out doctors moulded to this template, then we should expect a new generation of scholar saints and gentle scientists—wise, knowledgeable, sensitive, collegiate, humble, and good beyond imagining.

It is in the nature of every profession to set itself an ideal character and attempt to impose it as best it can on new entrants. It is also in the nature of humanity to fail that ideal most of the time. Visit any training establishment—of barristers, solicitors, police, nurses, or even journalists (a low trade, hardly a profession)—and you will find the most exalted sentiments imparted to …
A Birth in Tedda
Authors: Richard M. Hodes
Journal: Annals of Internal Medicine (1993)

On Being a Doctor1 May 1993A Birth in TeddaRichard M. Hodes, MDRichard M. Hodes, MDAmerican Joint Distribution Committee, Addis Ababa, Ethiopia.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-9-199305010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail A Western physician in rural Ethiopia finds himself helpless when a local woman insists on delivering a baby her own way. A chicken and frankincense are used to ward off an evil spirit, and the woman delivers a discourse on her delivery techniques.I had been in Tedda, a village in the northwest highlands of Ethiopia, for months, caring for several thousand Ethiopian Jews passing through a transit camp en route to Israel. They walked through mountain highlands and malarial lowlands for up to 3 weeks, armed and traveling in groups for protection from bandits and wild animals. The camp ... Author, Article, and Disclosure InformationAffiliations: American Joint Distribution Committee, Addis Ababa, Ethiopia.Corresponding Author: Richard M. Hodes, MD, American Joint Distribution Committee, P.O. Box 7600, Addis Ababa, Ethiopia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPregnancy and Delivery Practices and Beliefs of Ethiopian Immigrant Women in Israel 1 May 1993Volume 118, Issue 9Page: 738-740KeywordsBirthBloodBreathingCyclic adenosine monophosphateDeceptionHeart rateJewish peopleKneesPlacentaPregnancy Issue Published: 1 May 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma
Authors: A Bouchekioua, L Scourzic, O de Wever, Y Zhang, P Cervera, A Aline-Fardin, T Mercher, P Gaulard, R Nyga, D Jeziorowska, L Douay, W Vainchenker, F Louache, C Gespach, E Solary, P Coppo
Journal: Leukemia (2013)
IMMUNOLOGIC REJECTION OF DIETHYLNITROSAMINE-INDUCED HEPATOMAS IN STRAIN 2 GUINEA PIGS
Authors: Harold F. Dvorak, Ann M. Dvorak, Winthrop H. Churchill
Journal: The Journal of Experimental Medicine (1973)

The morphologic events associated with the immunologic rejection by strain 2 guinea pigs of ascites variants of two lines of diethylnitrosamine-induced tumors have been studied by light and electron microscopy. Tumor injection sites in the skin of control animals exhibited clusters of viable, actively mitotic tumor cells along with a modest inflammatory infiltrate composed of lymphocytes, macrophages, neutrophils, and rare basophils. In contrast, similar injections of either tumor line in specifically sensitized guinea pigs elicited typical delayed-type skin reactions associated with tumor cell necrosis and a more extensive inflammatory infiltrate including a selective increase in the number of basophilic leukocytes (12%, line 1, or 23%, line 10, of total inflammatory cells). That basophils may have a role in tumor resistance in vivo is suggested by the close anatomic associations observed between basophils and tumor cells, and by the fact that basophils were the only inflammatory cell to demonstrate a relative increase in frequency in the lesions of sensitized as compared with control animals. Moreover, intraperitoneal injection of line 1 tumor in specifically sensitized animals elicited a striking basophilia within 24 h. Unlike macrophages, basophils did not phagocytose tumor cells but did evidence occasional extrusion of granules and frequently exhibited loss of granule staining density, a change that may be related to release of mediator substances. Electron microscope studies of line 1 tumor rejection in the peritoneal cavities of specifically sensitized guinea pigs demonstrated aggregations of "activated" macrophages, lymphocytes, basophils, and damaged or dead tumor cells. These aggregates, held together by complex interdigitations of macrophage villi, closely resembled those occurring in vitro among peritoneal exudate cells whose migration from capillary tubes was inhibited by migration inhibition factor (MIF). Moreover, cells in these aggregates, as well as macrophages inhibited by MIF in vitro, lacked a normal coating of cell surface material.
ENDONASAL METHOD OF REMOVAL OF HYPOPHYSEAL TUMORSWITH REPORT OF TWO SUCCESSFUL CASES
Authors: OSKAR HIRSCH
Journal: JAMA (1910)

In his article on the surgery of the hypophysis from the standpoint of the rhinologist, Dr. J. M. West<sup>1</sup>mentioned the fact that "heretofore rhinologists have been interested in the hypophysis only in a general way." Later on in his article he describes a method by which he resects the septum endonasally, thereby reaching the sphenoid, which he opens widely, and through this opening reaches the hypophysis. Although Dr. West searched the German literature with great care concerning the operative treatment of hypophysis tumors, he neglected those publications which described the endonasal method, which was the most important to him. In March, 1909, I published a new method<sup>2</sup>of endonasal operation for the removal of hypophyseal tumors. This method is based on Hajek's<sup>3</sup>radical operation on the sphenoid sinus and is done in several sittings. It is performed in the following way: <h3>Operation.—</h3> Under cocain anesthesia the
Re: Noburu Numao, Satoru Kawakami, Minato Yokoyama et al. Improved Accuracy in Predicting the Presence of Gleason Pattern 4/5 Prostate Cancer by Three-Dimensional 26-Core Systematic Biopsy. Eur Urol 2007;52:1663–9
Authors: Rafael Boscolo-Berto, Antonio Galfano, Massimo Iafrate
Journal: European Urology (2008)
THE ROLE OF VASOCONSTRICTION IN THE LOCAL SHWARTZMAN REACTION
Authors: David P. Rall, Margaret G. Kelly
Journal: The Journal of Experimental Medicine (1957)

The local Shwartzman reaction was provoked in the skin of the ear, hind leg, and costovertebral angle of the rabbit, as well as in the ventral abdominal skin. Certain adrenergic blocking drugs reduced the incidence of positive reactions when given prior to the provocative dose of bacterial polysaccharide. Epinephrine and other vasoconstrictor drugs administered intradermally into the prepared skin site produced typical hemorrhagic-necrotic lesions when the usual intravenous injection of polysaccharide was omitted. This reaction could be blocked by adrenergic blocking drugs, but appeared to be augmented by heparin or nitrogen mustard. A hypothesis has been developed to help explain the mechanism of the local Shwartzman reaction. Following the preparatory dose, tissue metabolic changes occur which lead to increased lactic acid production and render the area particularly susceptible to anoxia. Following the provocative dose, adrenergic vasoconstriction occurs. It is suggested that this vasoconstriction may be intensified at the prepared site by small residual amounts of the preparatory dose of polysaccharide which might potentiate the action of the epinephrine. The anoxia initiated by the vasoconstriction is prolonged and intensified by the formation of intravascular thrombi around clumps of leucocytes and platelets. This anoxia, superimposed on the local metabolic changes, leads to the characteristic lesion of hemorrhage and necrosis. Thus a combination of factors, all of causal importance and largely due to known pharmacologic properties of bacterial lipopolysaccharide, occur in specific sequence to lead to the classic local Shwartzman reaction.
THE EARLY DIAGNOSIS OF JOINT TUBERCULOSIS
Authors: ALAN DeFOREST SMITH
Journal: JAMA (1924)

Late cases of tuberculosis of joints, in which destruction has taken place, offer comparatively little difficulty in diagnosis, although not a few of these, so-called, at operation prove to be some other pathologic condition. Early cases, however, by which is meant those in the first year or two of the disease, are exceedingly difficult to diagnose, and are the source of a high percentage of error. The experience in this clinic has led to the belief that in many of these cases a positive diagnosis cannot be made by the ordinary methods so far in general use. For this reason, it has become our routine to do exploratory operations in all doubtful cases. Not only are cases of tuberculosis commonly mistaken for some other condition, such as chronic arthritis or synovitis, but other conditions are considered as tuberculosis and treated as such. It is difficult to decide which error causes
Diagnosis and Treatment of Erythema Induratum (Bazin)
Authors: M. Feiwel, D. D. Munro
Journal: BMJ (1965)

Crushed Chest Injury-Reid and Baird MEDBRITJOURNAL suggested based principally on the degree of abnormality of blood-gas levels, and not on the extent of thoracic bony injuries.A series of 33 cases treated in the Respiratory Emergency Unit of Glasgow Royal Infirmary is presented and briefly discussed.A plea is made for frequent blood-gas analysis in the assessment of treatment of these cases.We are grateful to Dr. A. C. Forrester and Dr. D. Campbell
Association of Remnant Lipoprotein Levels With Impairment of Endothelium-Dependent Vasomotor Function in Human Coronary Arteries
Authors: Kiyotaka Kugiyama, Hideki Doi, Takeshi Motoyama, Hirofumi Soejima, Kenji Misumi, Hiroaki Kawano, Osamu Nakagawa, Michihiro Yoshimura, Hisao Ogawa, Toshiyuki Matsumura, Seigo Sugiyama, Takamitsu Nakano, Katsuyuki Nakajima, Hirofumi Yasue
Journal: Circulation (1998)

Background —It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. Methods and Results —The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 μg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti–apolipoprotein (apo) A-1 and anti–apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of N G -monomethyl- l -arginine (50 μmol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. Conclusions —Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.
Value of family history in identifying women at risk of venous thromboembolism during oral contraception: observational study
Authors: B. Cosmi
Journal: BMJ (2001)

Common inherited thrombophilic defects such as factor V Leiden and G20120A mutation of the prothrombin gene interact synergistically with oral contraceptives to increase the risk of venous thromboembolism. 1 2 The best approach to identify women at higher risk of venous thromboembolism before taking oral contraceptives is controversial.Universal screening is not cost effective because 8000 women need to be screened for factor V Leiden to detect 400 mutations and prevent one episode of venous thromboembolism. 1 Many authors recommend selective screening in women with a personal or family history of venous thromboembolism. 1 However, the effectiveness of this approach has not been proved.The aim of our study was to evaluate the sensitivity and positive predictive value of a family history of venous thromboembolism for identifying common thrombophilic defects in women without thrombosis before taking oral contraceptives.
Exercise-induced anaphylactic reaction to hazelnut
Authors: F. Martín Muñoz, J. M. López Cazaña, F. Villas, J. F. Contreras, J. M. Díaz, J. A. Ojeda
Journal: Allergy (1994)

Reproducible, exercise‐induced anaphylactic reactions occur in some patients only after certain foods have been eaten before exercise. We describe a patient in whom hazelnuts were a triggering factor for exercise‐induced anaphylaxis. Skin tests and RAST were positive for nuts and grass and weed pollen. The exercise challenge test after hazelnut ingestion was positive. Food hypersensitivity should be investigated in all cases of exercise‐induced anaphylaxis.
Epidemiology of anaphylaxis in Siriraj Hospital
Authors: W. Bunsawansong, O. Jirapongsananuruk, N. Visitsunthorn, P. Vichyanond
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: Anaphylaxis is a medical emergency. Awareness of its' clinical features and causes is important. Identifiable causes must be avoided for the prevention of recurrence. There are few epidemiological studies on anaphylaxis. We report, herein, the epidemiology of anaphylaxis in Siriraj Hospital, Thailand. METHODS: We studied 130 patients with anaphylaxis presented to Siriraj Hospital between 1993 through 2004 by chart review, direct patient interview, physical examination, and laboratory test, when possible. RESULTS: Mean age of patients was 23.40 years ± 21.59 years (range, 2.76 months to 81.31 years) with male: female ratio of 1.05:1. The occurrence rate was 2.91 per 100,000 person-years. The incidence rate was 2.32 per 100,000 person-years. Initial symptoms were limited to skin in 65.89 % (urticaria/ angioedema), respiratory 17.05 %, cardiovascular 9.30 %, and gastrointestinal 7.75 %. Anaphylaxis commonly occurred in April (14.81%), May (10.49%), and October (10.49%). Site of exposure was at home (58.14%), hospital (34.11%) and school/ office (3.10%). Fifty-five percents of patients were atopic. Identifiable causes were drug (35.66%), food (28.68%), idiopathic (14.73%), and insect (10.85%). Peanut was not found to be the causes of anaphylaxis in this study. Anaphylaxis was diagnosed in the 1stepisode in 75 % of cases, the 2ndepisode in 8.82 %, and more than 2ndepisode in 10.24 %. Epinephrine was given in only 68.99% of cases. Admission rate was 69.12 % (included observed-room admission). One patient died. CONCLUSIONS: Anaphylaxis is under-recognized in Thailand. Although the incidence in this study was less than 1%. One patient died.