tbuckley/cabot-search huggingface dataset:
Unnecessary polypharmacy for epilepsy.
Authors: S D Shorvon, E H Reynolds
Journal: BMJ (1977)

A retrospective survey of 50 adult epileptic outpatients who were taking two anticonvulsants drugs showed that seizure control had improved in the six months after the introduction of the second drug in only 36%. When blood concentrations of the two anticonvulsants were subsequently measured improvement in seizure control was found to be significantly related to the presence of optimum blood concentrations of at least one drug. Much unnecessary polypharmacy in the treatment of epilepsy could be avoided by ensuring an optimum blood concentration of one drug before considering the addition of a second.
Membrane phosphorylation protects the cardiac sarcoplasmic reticulum Ca2+-ATPase against chlorinated oxidants in vitro
Authors: Alexander Y Antipenko, Madeleine A Kirchberger
Journal: Cardiovascular Research (1997)

Objective: The calcium (Ca) pump of cardiac sarcoplasmic reticulum (SR) membranes is vulnerable to oxidation and hence likely to be damaged by chlorinated compounds, specifically hypochlorite (NaOCl) and monochloramine (NH2Cl), the most potent oxidants produced upon neutrophil activation. This could occur during prolonged ischemia or myocardial infarction when tissue levels of catecholamines are high. Phospholamban (PLN), the phosphorylatable regulator of the Ca pump, plays a central role in the effects of β-adrenergic agonists on the heart. The purpose of this study was to investigate a possible role of PLN in determining the pump's sensitivity to NaOCl and NH2Cl. Methods: Ca-uptake and Ca2+-ATPase activities in purified phosphorylated and control canine cardiac microsomes, incubated at increasing concentrations of NaOCl or NH2Cl, were related to the extent of PLN phosphorylation by protein kinase A, which was quantitated by PhosphorImager analysis. Results and Conclusions: Our data indicate that microsomal phosphorylation protects the Ca pump fully against 10 μM NaOCl or NH2Cl, which inhibit Ca-uptake by 21–41% when assayed at 25 or 37°C and saturating Ca2+ in unphosphorylated microsomes, and protects partially at higher oxidant concentrations. The protective effect of protein kinase A on Ca-uptake is proportional to the amount of phosphorylated PLN. No comparable protection against similar oxidative damage of the Ca pump is observed when light fast skeletal muscle microsomes, which lack PLN, are incubated under conditions favorable for phosphorylation nor when PLN's inhibition of the cardiac Ca pump is relieved by proteolytic cleavage of its cytoplasmic domain. Our findings contribute toward an understanding of possible endogenous protective mechanisms that may promote calcium homeostasis in myocardial cells in inflammatory states associated with neutrophil activation and may suggest an approach toward development of protective strategies against oxidative damage in the heart.
?- but not ?-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism
Authors: B RORABAUGH, S ROSS, R GAIVIN, R PAPAY, D MCCUNE, P SIMPSON, D PEREZ
Journal: Cardiovascular Research (2004)

Brief periods of ischemia stimulate an endogenous mechanism in the heart that protects the myocardium from subsequent ischemic injury. alpha1-Adrenergic receptors (ARs) have been implicated in this process. However, the lack of sufficiently selective antagonists has made it difficult to determine which alpha1-AR subtype protects the heart from ischemic injury. The goal of this study was to identify the alpha1-AR subtype that is involved in ischemic preconditioning. We developed transgenic mice that express constitutively active mutant (CAM) forms of the alpha1A-AR or the alpha1B-AR regulated by their endogenous promoters. Hearts isolated from transgenic and non-transgenic mice were perfused by the Langendorff method using an ischemic preconditioning perfusion protocol or a non-preconditioning perfusion protocol prior to 30-min ischemia and 40-min reperfusion. Contractile function was continuously monitored through an intraventricular balloon. The contractile function of non-transgenic hearts perfused according to the ischemic preconditioning protocol completely recovered from 30-min ischemia. However, non-transgenic hearts perfused according to the non-preconditioning protocol recovered only 60% of their contractile function. The contractile function of CAM alpha1A-AR hearts, but not CAM alpha1B-AR hearts, completely recovered from 30-min ischemia even though they were perfused according to the non-preconditioning protocol. Thus, CAM alpha1A-AR hearts, but not CAM alpha1B-AR hearts, were inherently preconditioned against ischemic injury. Staurosporine, but not chelerythrine, completely reversed the preconditioning effect of CAM alpha1A-ARs. These data demonstrate that alpha1A-ARs protect the heart from ischemic injury through a staurosporine-sensitive signaling pathway that is independent of protein kinase C.
Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma
Authors: F Jundt, Ö Acikgöz, S-H Kwon, R Schwarzer, I Anagnostopoulos, B Wiesner, S Mathas, M Hummel, H Stein, H M Reichardt, B Dörken
Journal: Leukemia (2008)
The conflict and paradox of medical practice and corporate medicine.
Authors: L Kahn
Journal: Circulation (1986)

AMERICAN MEDICINE functions in an incongruous environment.The humanistic and intellectual chal- lenges of a medical career have never been more stim- ulating, yet applications for admission to medical schools have been decreasing.Research activities are productive but financial support is reduced.Business and government impose competition and regulation on a profession whose purpose is to help the sick.The benefits of scientific and technical medicine are eager- ly sought by the American people while the compe- tence of doctors is challenged by a litigious society.This dichotomy of a profession growing rapidly in capability while decreasing in autonomy is the outcome of major shifts in the cultural and economic value of health services to the American people in the past three decades.Fuchs' has described them well.The major force currently appears to be economic rath- er than cultural, with emphasis on competition and regulation.These changes and their causes are not new to economists and social theorists; but, only recently has the influence of these socioeconomic events begun to be evident to practicing doctors.The impact univer- sally affects medical practice and bears directly on the concept of professional behavior.It continues at a rap- id pace and with increasing strength.It is essential that physicians (1) recognize the socio-economic factors that shaped the health care marketplace, (2) understand the implications of the current transmutations in health care delivery, particularly as they apply to the private practitioner, and (3) protect their professional role in the new world of medical practice.Socioeconomic factors that shaped the health care mar- ketplace.Health care is the fourth largest area of our economy and in recent years has expanded more than any component of the Consumer Price Index.2It has increased from 4.4%3 of the Gross National
Gallium-67 Scintigraphy in Well-differentiated Lymphocytic Lymphoma of the Skin
Authors: ROSWELL N. BECK, RALPH BLUMHARDT, WILLIAM BENNETT, HAROLD CABLE, RONALD McCAULEY, ROBERT J. TELEPAK, JAMIE PACHECO, LLOYD PHILLIPS
Journal: Clinical Nuclear Medicine (1985)

Skin lymphomas are now divided into “T” or thymic cell lymphomas (mycosis fungoides being the principal type) and “B” cell lymphomas after the bursa of Fabricius. The “T” cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed “B” cell lymphomas. A large percentage of these non “T” cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.
The Doppler Pattern of Pulmonic Insufficiency in Normal Subjects
Authors: W. KOSTUCKI
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 February 1986The Doppler Pattern of Pulmonic Insufficiency in Normal SubjectsW. KOSTUCKI, M.D., J.-L. VANDENBOSSCHE, M.D., M. ENGLERT, M.D.W. KOSTUCKI, M.D.Search for more papers by this author, J.-L. VANDENBOSSCHE, M.D.Search for more papers by this author, M. ENGLERT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-2-284_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Pérez and associates (1) have used Doppler echocardiography, in a very elegant way, to demonstrate the pulmonic origin of the diastolic murmurs commonly found in patients with renal failure. In their control group of 15 healthy persons, 3 (20%) had pulmonic insufficiency detectable by Doppler techniques that occupied 25 ± 12% (SD) of the diastole with peak flow velocity averaging 0.8 ±0.2 m/s.In a recent study of pulsed Doppler insufficiency patterns in normal persons (mean age, 24; range, 15 to 48), we found a regurgitant turbulent pulmonic flow pattern in 23 of 25 persons (92%)...References1. PÉREZSMITHMELTZER JCV. Pulmonic valve insufficiency: a common cause of transient diastolic murmurs in renal failure. Ann Intern Med. 1985;103:497-502. LinkGoogle Scholar2. KOSTUCKIVANDENBOSSCHEFRIARTENGLERT WJAM. Pseudoregurgitant flow patterns in normal individuals: a pulsed Doppler study [Abstract]. J Cardiovasc Ultrasound. 1985;4:4. Google Scholar3. YOCKNAASZSCHNITTGERPOPP PCIR. Doppler tricuspid and pulmonic regurgitation in normals: is it real [Abstract]? Circulation. 1984;70 (4 pt 2): II-40. Google Scholar4. TAKAOMIYATAKEIZUMIKINOSHITASAKAKIBARANIMURA SKSNHY. Physiological pulmonary regurgitation detected by the Doppler technique and its differential diagnosis [Abstract]. J Am Coll Cardiol. 1985;5:499. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hôpital Universitaire Saint Pierre B-1000 Brussels Belgium PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1986Volume 104, Issue 2Page: 284-285KeywordsDiastoleEchocardiographyRenal failure Issue Published: 1 February 1986 PDF DownloadLoading ...
Smoking and ulcerative colitis.
Authors: D R Perera, C M Janeway, A Feld, J T Ylvisaker, L Belic, H Jick
Journal: BMJ (1984)

Smoking and ulcerative colitis D R Perera, md, and others. 1533 Treatment of end stage renal disease A Nicholls, mrcp, and T Feest, mrcp. . .. 1533 Benzodiazepines on trial D E Price, mrcp, and others. 1534 Prescription charges bring hardship J T Hart, frcgp. 1534 Poor management of unconscious rugby player watched by millions DAD Macleod, frcs. 1534 Quality control of home monitoring of blood glucose concentrations P H Winocour, mrcp, and G A McKinnon, bsc; W N Trounson, mrcp, and others; J Anderson, mrcp, and Eva Kohner, frcp 1535 Guidelines for initial management after head injury J Pilpel, bm; B Jennett, frcs. 1536 Policies on prevention D P St George, MB. 1536 Tremor L J Findley, mrcp, and Lynn Cleeves, bsc 1536 British cosmetic regulations inadequate Catherine Ridley, MB, and others. 1537 The use of a conical spacer after laryng?e to my P A Webber, frcs, and A R Brown, MB.. 1537 Haemoptysis during sexual intercourse T K Daneshmend, mrcp. 1537 Haematemesis and ectopic pregnancy E J Thomas, mrcog. 1537 Scoring system to improve cost effectiveness of open access endoscopy S Huck, MB, and others. 1538 Syncope and mitral valve prolapse in the army P Lynch, mrcp, and N Ineson, mrcp. . .. 1538 Treatment of prolactinomas with megavoltage radiotherapy G Teasdale, frcsed, and others. 1538 Conservative management of pregnancy in diabetic women J M Stronge, frcog, and M I Drury, md 1539 Cash limits and other matters P V Scott, FFARCS. 1539
Localization of Cardiac Sodium Channels in Caveolin-Rich Membrane Domains
Authors: Tracy L. Yarbrough, Tong Lu, Hon-Chi Lee, Erwin F. Shibata
Journal: Circulation Research (2002)

This study demonstrates that caveolae, omega-shaped membrane invaginations, are involved in cardiac sodium channel regulation by a mechanism involving the α subunit of the stimulatory heterotrimeric G-protein, Gα s , via stimulation of the cell surface β-adrenergic receptor. Stimulation of β-adrenergic receptors with 10 μmol/L isoproterenol in the presence of a protein kinase A inhibitor increased the whole-cell sodium current by a “direct” cAMP-independent G-protein mechanism. The addition of antibodies against caveolin-3 to the cell’s cytoplasm via the pipette solution abrogated this direct G protein-induced increase in sodium current, whereas antibodies to caveolin-1 or caveolin-2 did not. Voltage-gated sodium channel proteins were found to associate with caveolin-rich membranes obtained by detergent-free buoyant density separation. The purity of the caveolar membrane fraction was verified by Western blot analyses, which indicated that endoplasmic/sarcoplasmic reticulum, endosomal compartments, Golgi apparatus, clathrin-coated vesicles, and sarcolemmal membranes were excluded from the caveolin-rich membrane fraction. Additionally, the sodium channel was found to colocalize with caveolar membranes by immunoprecipitation, indirect immunofluorescence, and immunogold transmission electron microscopy. These results suggest that stimulation of β-adrenergic receptors, and thereby Gα s , promotes the presentation of cardiac sodium channels associated with caveolar membranes to the sarcolemma.
“Defragmenting” the noninvasive diagnosis of nonalcoholic steatohepatitis: Hopes from cytokeratin-18
Authors: Yusuf Yilmaz
Journal: Hepatology (2009)

The multicenter study by Feldstein and colleagues1 on the usefulness of caspase-generated cytokeratin-18 (CK-18) fragments in the noninvasive diagnosis of nonalcoholic steatohepatitis (NASH) is definitely interesting. The authors convincingly demonstrated that elevated levels of CK-18 fragments, which serve as markers of hepatocyte apoptosis, are a strong and independent biochemical correlate of NASH, as well as of the presence of liver fibrosis. These results confirm and expand our original observation that CK-18 fragments might serve to noninvasively distinguish steatohepatitis in the setting of nonalcoholic fatty liver disease.2 Altogether, these findings hold great promise to downgrade the role of invasive liver biopsy as the only reliable way of diagnosing NASH and monitoring disease progression. Of note, the authors have also provided evidence that the addition of routinely available laboratory tests did not significantly improve the sensitivity and specificity of CK-18 fragments to diagnose NASH.1 It is possible, however, that the addition of biomarkers that cover different pathophysiological facets of steatohepatitis (beside hepatocyte apoptosis) may further improve the diagnostic ability of CK-18 fragments. In this regard, it would be interesting to analyze the predictive value of CK-18 fragments in relation to biomarkers associated with the metabolic facets of NASH, i.e., novel biochemical markers of the metabolic syndrome that have been proven to be valuable tools to identify patients with NASH, such as soluble RAGE (receptor for advanced glycation end-products)3 and pentraxin 3.4 The promise for the future is not only to further validate the clinical usefulness of existing biomarker panels for NASH incorporating measurements of CK-18 fragments,5 but also to develop novel combinations of different enzyme-linked immunosorbent assay–based assays with improved sensitivity and specificity that may definitely reduce the need for liver biopsies. Yusuf Yilmaz M.D.*, * Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey.
Syncopal attacks as symptom of severe coronary artery disease.
Authors: J B Irving, A H Kitchin
Journal: BMJ (1975)

by T.L.C.) from abnormal cells contained about six times as much 14C-palmitate after five days in culture as did that from control cells.Addition of L-carnitine to the cultures (0-2 g/l of medium) did not modify the enhanced rate of incorporation of "4C-palmitate into triglyceride by the abnormal cells.
The accuracy of activated partial thromboplastin times when drawn through a peripherally inserted central catheter
Authors: Matthew T. Rondina, Boaz Markewitz, Stephen J. Kling, Robert Nohavec, George M. Rodgers
Journal: American Journal of Hematology (2007)

Abstract The peripherally‐inserted central catheter (PICC) is used commonly in hospitalized patients. The presence of heparin within the PICC lumen, however, may affect the results of coagulation indices when measured on blood drawn through it. In 41 patients with a PICC inserted as part of their medical care, we compared activated partial thromboplastin times (aPTTs) measured on blood drawn through the PICC to blood drawn through a peripheral venipuncture (VP). There were no clinically significant differences between aPTT values from the two samples. Using the PICC to obtain blood for the measurement of aPTT is accurate and may reduce the need for peripheral VPs. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort
Authors: Dorothee M. Baur, Jens Klotsche, Ole-Petter R. Hamnvik, Caroline Sievers, Lars Pieper, Hans-Ulrich Wittchen, Günter K. Stalla, Roland M. Schmid, Stefanos N. Kales, Christos S. Mantzoros
Journal: Metabolism (2010)
Abstract AL-1: AACR outstanding investigator award for breast cancer research: Understanding estrogen receptor transcription in breast cancer
Authors: JS Carroll
Journal: Cancer Research (2013)

Abstract Estrogen Receptor (ER) is the defining feature of luminal breast cancers, where is functions as a transcription factor. The traditional view of ER getting recruited to promoters of target genes is too simplistic. The recent discovery of ER-DNA interaction regions from ER+ breast cancer cell lines has revealed that ER rarely associates with promoter regions of target genes and instead associates with enhancer elements significant distances from the target genes. The genomic mapping of ER binding events also revealed the enrichment of DNA motifs for Forkhead factors. The Forkhead protein FoxA1 (HNF3a) was subsequently shown to bind to half of the ER binding events in the genome and was required for ER to maintain interaction with DNA. We have extended on these findings to explore ER and FoxA1 functional interactions in breast cancer, with a specific focus on changes in binding dynamics that occur during endocrine resistance. To this end, we have established transcription factor mapping approaches (ChIP-seq) in primary tumor material, to investigate differential ER/FoxA1 binding that occurs during tumor progression. We have functionally explored underlying factors that contribute to altered transcription factor binding and activity. In addition, we have recently established a method for rapid unbiased discovery of protein interacting complexes, which we have applied to discover ER associated proteins. We find an unexpected interaction between ER and progesterone receptor (PR) in ER+ breast cancer. We show that PR is a negative regulator of the ER complex, where it is important for modulating ER-DNA interactions and cellular growth. These findings help delineate the complexes that influence ER transcriptional activity and ultimately impinge on tumor progression and drug sensitivity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr AL-1.
Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients
Authors: Hugh S. Taylor
Journal: JAMA (2004)

Regeneration of the endometrium in each menstrual cycle is required for reproduction. Endogenous endometrial stem cells reside in the basalis layer and serve as a source of cells that differentiate to form the endometrium. Bone marrow-derived cells have been shown to take on functions outside the hematopoietic system.To investigate the possibility that cells of extrauterine origin could repopulate the endometrium.Endometrium from 4 HLA-mismatched bone marrow transplant recipients (1998-2002) was evaluated for donor HLA expression. Each recipient had a bone marrow donor with an HLA type that enabled determination of the origin of any cell. Endometrial biopsies also were obtained from 4 healthy control women.HLA type was determined by immunohistochemistry and by reverse transcription-polymerase chain reaction.Donor-derived endometrial cells were detected in endometrial biopsy samples from all bone marrow recipients and accounted for 0.2% to 48% of epithelial cells and 0.3% to 52% of stromal cells. None of the controls demonstrated HLA mismatch in endometrial samples.These findings demonstrate that endometrial cells can originate from donor-derived bone marrow cells and suggest that nonuterine stem cells contribute to the regeneration of endometrial tissue.
Selective T-cell ablation with bismuth-213–labeled anti-TCRαβ as nonmyeloablative conditioning for allogeneic canine marrow transplantation
Authors: Wolfgang A. Bethge, D. Scott Wilbur, Rainer Storb, Donald K. Hamlin, Erlinda B. Santos, Martin W. Brechbiel, Darrell R. Fisher, Brenda M. Sandmaier
Journal: Blood (2003)
TREATMENT OF TYPHOID FEVER.
Authors: FRANK BILLINGS
Journal: JAMA (1900)

Typhoid fever is an acute infectious fever, caused by a specific microbe—the bacillus typhosus. It is a filth disease and a so-called water-borne infection. The bacterium gains access to the body, in the great majority of cases, through the ingesta. Water is the usual carrier. Contaminated milk or other food, and dust laden with the bacillus, either inhaled or swallowed, are sources of the infection. Upon the local and state boards of health devolves the question of the manner of typhoid contamination of water and food and the measures which may correct the evil. Upon the practitioner, however, falls a responsibility which is very important in respect to prophylaxis. The bacillus finds egress from the body of the patient chiefly by the feces and the urine. The infected excreta may contaminate all objects and materials with which they come in contact. The soiled person and clothing of the patient and
Adrenocortical Hormones in Human Hypertension and Their Relation to Angiotensin
Authors: J. GENEST, P. BIRON, E. KOIW, W. NOWACZYNSKI, M. CHRÉTIEN, R. BOUCHER
Journal: Circulation Research (1961)

In summary, we have demonstrated that: (a) Infusions of epinephrine, norepinephrine, and phenylephrine in 5 per cent glucose for 7 to 10 hours have little effect on, or decrease, urinary aldosterone excretion. (b) Angiotensin II infusions markedly decrease sodium excretion and the Na/K ratio and increase the excretion of aldosterone; of its ring-A reduced metabolite, pregnane-3-α,18,21-triol,11,20-dione; and, to a much lesser degree, of cortisol and tetrahydrocortisone in all normal subjects studied. (c) In patients with benign essential hypertension, infusions of angiotensin also stimulate urinary aldosterone excretion hut have a completely opposite effect on electrolytes-that of increasing sodium output and the Na/K ratio. This basic difference in response to angiotensin points to a fundamental problem to be solved for a better understanding of the disease. It is felt that the relative or absolute excess of aldosterone over progesterone secretion may be the important adrenal disturbance among the basic factors involved in the pathogenesis of arterial hypertension. This disturbance is definitely linked with angiotensin and sodium regulation.