tbuckley/cabot-search huggingface dataset:
Lasker Award Often Prologue to Nobel Prize
Authors: Lori E. Marks
Journal: JAMA (1989)

THIS FALL's Lasker Awards presentations are the 44th in the series. The awards are given through the Albert and Mary Lasker Foundation, established in 1946 and dedicated to honoring scientists whose research accomplishments are particularly outstanding. In addition, the foundation encourages support of major medical scientific efforts such as those of the National Institutes of Health (Bethesda, Md) and educates the public about the importance of such research. The Albert Lasker Awards Program gives three awards honoring "individuals who have made contributions in basic and clinical research in the diseases which are the main causes of death and disability." The foundation lists these "main causes" in the United States as cardiovascular, neoplastic, mental, respiratory, joint, and neurological diseases. For the last 25 years, the awards have been presented for basic medical and clinical research and public service. In the past, Lasker awards were also given for medical journalism and public
Complaint-Oriented Clinics
Authors: David A. Drachman
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Dr. Jaffee's EDITORIAL (224:897, 1973) makes some interesting observations about the need for a critical appraisal of " `complaint-centered' clinics," and contains some good, old-fashioned common sense about the need for "skillful individual physicians" who will " `treat the person, not the symptom.' " His concern that such clinics might divert patients from the more usual health delivery setting, yet fail to provide any additional benefits is worthy of consideration. Unfortunately, he provides a poorly balanced critique of the complaint-oriented clinics in which he considers only their shortcomings and fails to appreciate the value of the highly organized evaluation (or treatment) that may be conducted in such a setting. For more than three years, we have maintained a "dizziness clinic" at Northwestern University Medical School, designed to organize an approach to the exceedingly complex and extensive series of disorders that lie at the root of the unitary complaint of "dizziness".
Making better use of our nurses.
Authors: H W Acheson
Journal: BMJ (1977)

distances and stay away from home as before.I suggest that specialist societies should urgently consider amalgamation or combined meetings with the larger organisations.Unless something is done to reduce expenses I feel sure that resignations will inevitably follow non-attendance and many of these valuable professional activities will cease.Little help can be expected from employing authorities, whose funds are wholly insufficient to cover meeting expenses for most of their staff.
Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1beta in macrophages.
Authors: B G Ohlsson, M C Englund, A L Karlsson, E Knutsen, C Erixon, H Skribeck, Y Liu, G Bondjers, O Wiklund
Journal: Journal of Clinical Investigation (1996)

A large body of evidence suggests that oxidized LDL (oxLDL) has a role in atherogenesis. One effect is the impact on macrophage function. We have studied the effects of oxLDL and oxysterols on the binding of the transcription factors nuclear factor (NF)-kappaB and AP-1 to DNA. These transcription factors are involved in the regulation of several genes and expressed during activation of macrophages, for example by endotoxin (LPS). OxLDL did not induce binding of NF-kappaB. However, the LPS-induced response to NF-kappaB was substantially reduced after preincubation with oxLDL. Medium and highly oxidized LDL also decreased the constitutive DNA-binding of AP-1. Similar effects on AP-1-binding were seen with the oxysterols, 7beta-hydroxycholesterol, 24- hydroxy-, 25-hydroxy-, and 27-hydroxy-cholesterol. Our data therefore suggest an effect of oxLDL on the DNA-binding of AP-1, which might be mediated by the oxysterol content of oxLDL. A decreased LPS-induced TNF-alpha and IL-1beta mRNA and protein expression were found in macrophages incubated with oxLDL before LPS-exposure. These observations suggest that macrophages that internalize extensively oxidized LDL are suppressed in their response to inflammatory stimulation.
Mechanistic Role of <i>I</i> <sub>f</sub> Revealed by Induction of Ventricular Automaticity by Somatic Gene Transfer of Gating-Engineered Pacemaker (HCN) Channels
Authors: Tian Xue, Chung-Wah Siu, Deborah K. Lieu, Chu-Pak Lau, Hung-Fat Tse, Ronald A. Li
Journal: Circulation (2007)

Although I(f), encoded by the hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channel gene family, is known to be functionally important in pacing, its mechanistic action is largely inferential and indeed somewhat controversial. To dissect in detail the role of I(f), we investigated the functional consequences of overexpressing in adult guinea pig left ventricular cardiomyocytes (LVCMs) various HCN1 constructs that have been engineered to exhibit different gating properties.We created the recombinant adenoviruses Ad-CMV-GFP-IRES (CGI), Ad-CGI-HCN1, Ad-CGI-HCN1-delta delta delta, and Ad-CGI-HCN1-Ins, which mediate ectopic expression of GFP alone, WT, EVY235-7delta delta delta, and Ins HCN1 channels, respectively; EVY235-7delta delta delta and Ins encode channels in which the S3-S4 linkers have been shortened and lengthened to favor and inhibit opening, respectively. Ad-CGI-HCN1, Ad-CGI-HCN1-delta delta delta, and Ad-CGI-HCN1-Ins, but not control Ad-CGI, transduction of LVCMs led to robust expression of I(f) with comparable densities when fully open (approximately = -22 pA/pF at -140 mV; P>0.05) but distinctive activation profiles (V(1/2) = -70.8+/-0.6, -60.4+/-0.7, and -87.7+/-0.7 mV; P<0.01, respectively). Whereas control (nontransduced or Ad-CGI-transduced) LVCMs were electrically quiescent, automaticity (206+/-16 bpm) was observed exclusively in 61% of Ad-HCN1-delta delta delta-transduced cells that displayed depolarized maximum diastolic potential (-60.6+/-0.5 versus -70.6+/-0.6 mV of resting membrane potential of control cells; P<0.01) and gradual phase 4 depolarization (306+/-32 mV/s) that were typical of genuine nodal cells. Furthermore, spontaneously firing Ad-HCN1-delta delta delta-transduced LVCMs responded positively to adrenergic stimulation (P<0.05) but exhibited neither overdrive excitation nor suppression. In contrast, the remaining 39% of Ad-HCN1-delta delta delta-transduced cells exhibited no spontaneous action potentials; however, a single ventricular action potential associated with a depolarized resting membrane potential and a unique, incomplete "phase 4-like" depolarization that did not lead to subsequent firing could be elicited on simulation. Such an intermediate phenotype, similarly observed in 100% of Ad-CGI-HCN- and Ad-CGI-HCN1-Ins-transduced LVCMs, could be readily reversed by ZD7288, hinting at a direct role of I(f). Correlation analysis revealed the specific biophysical parameters required for I(f) to function as an active membrane potential oscillator.Our results not only contribute to a better understanding of cardiac pacing but also may advance current efforts that focus primarily on automaticity induction to the next level by enabling bioengineering of central and peripheral cells that make up the native sinoatrial node.
1022-85 Glucose-insulin-potassium infusion improves myocardial salvage in diabetic patients with acute myocardial infarction treated with reperfusion therapy
Authors: Jürgen Pache, Joerg Hausleiter, Adnan Kastrati, Julinda Mehilli, Hildegard Bolwein, Helmut Schühlen, Josef Dirschinger, Albert Schoemig
Journal: Journal of the American College of Cardiology (2004)
Recombinant Erythropoietin and Medicare Payment
Authors: Jane E. Sisk
Journal: JAMA (1991)

The biologic recombinant human erythropoietin provides a recent case study of the great influence federal policies, especially Medicare payment, exert over the use and cost of medical technologies. By covering most dialysis patients, Medicare has been the predominant payer for recombinant erythropoietin, which corrects anemia associated with chronic renal disease. Medicare's leverage seems to have produced a low US price for the product. Paying a fixed rate per treatment with the biologic agent gave dialysis facilities a financial incentive to use low doses, but Medicare did not routinely monitor patients' responses. By August 1990, average and modal doses were low, and fewer than 45% of patients who had been treated for 6 months or more had ever attained the target hematocrit. Medicare should recognize the financial incentives of its payment policies and routinely evaluate the quality of care for beneficiaries.
Ultramicroscopic Structure of the Rheumatoid Nodule
Authors: W. Cochrane, D. V. Davies, J. Dorling, E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1964)

Berkshirewith Scharlach R for lipids.The tissue for electron microscopy was fixed with minimum delay in I per cent.osmium tetroxide, buffered at pH 7-4 (Zetterquist, 1956) for 1 to 2 hours, dehydrated 345 copyright.
Changes in Free Amino Acids in the Plasma during Hepatic Coma
Authors: Chung Wu, Jesse L. Bollman, Hugh R. Butt
Journal: Journal of Clinical Investigation (1955)

Previous reports frmm various laboratories have ances of protein metabolism, which emphasized the failure to demonstrate consistent and significant biochenjicalchanages during hepatic coma (1-3).However, a cross increase of amino acids in the plasma, urine and spinal fluid (4, 5) and an elevation of ammonia in the blood (6-9) have been observed to accompany hepatic coma.Since diseases of the liver often result in disturb- ' The Mayo Foundation, Rochester, Minnesota, is a part of the Graduate School of the University of Min- nesota.are usually manifested by a change in-the concentration of amino acids in the plasma, it was felt that a quantitative study of individual amino acids in patients in various stages of hepatic coma might -provide some information to elucidate the relationship between the biochemical and clinical findings.The results of such a study, which are presented in this report, indicate that the content of free amino acids in theblood was usually increased during severe hepatic disease.Increases in some or all of TABLE I Summary of the case histories of the patients Coma Age Pre-Case (Yrs.)Sex coma Light Deep Condition of patient 1 65 M X Acute viral hepatitis; moderate jaundice; condition fairly good and patient never beyond drowsy state; complete
Health professionals question "star ratings" for NHS
Authors: A. Gulland
Journal: BMJ (2002)

The best performing hospitals in England are to be awarded up to £1m ($1.6m; €1.6m) each in the wake of government league tables published last week.

The performance tables give 46 acute trusts a three star rating (highest rating), 77 two stars (“performing well”), and 35 a single star (“cause for concern”). Eight trusts are judged to be so poor that they are given no stars. Health secretary Alan …
Progress in Gastroenterology
Authors: Leslie J. Schoenfield
Journal: JAMA (1969)

The rapidity of progress in gastroenterology renders impossible the task of complete coverage in a single text and at the same time emphasizes the need for a compendium of new information. One logical solution to this dilemma is a series of "progress" volumes patterned as this text. Dr. Glass has called upon 32 authors to prepare 20 papers; 11 under the heading "stomach and esophagus," 5 on small intestine, 2 on colon, and 1 each on pancreas and mesenteric vasculature. The editor's interests have led to an admittedly unbalanced presentation, and this first volume emerges as a group of essays on selected topics by authorities in their fields. The authors, because of their expertise, have been able to filter much information, to present their concepts of the progress and current status. The text is well published and the tables, graphs, and illustrations carefully selected and reproduced. The individual papers vary
Cluster headache and herpes simplex: an association?
Authors: R Joseph, F C Rose
Journal: BMJ (1985)

Cluster headache and herpes simplex: an association?A patient presented with cluster headache occurring in association with ipsilateral facial herpes simplex.This suggested that the localised vasodilatation seen during an attack ofcluster headache may result from an axonal reflex activated by a latent viral infection in the trigeminal system.
Independent predictors of long-term results after balloon pulmonary valvuloplasty. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry Investigators.
Authors: B W McCrindle
Journal: Circulation (1994)

BACKGROUND This study was performed to determine independent predictors of long-term outcome after percutaneous balloon dilation of congenital pulmonary valve stenosis. Smaller follow-up series of patients after balloon pulmonary valvuloplasty have shown inconsistent results regarding the independent relation between prognostic factors and long-term outcome, as many patient selection and technical factors are correlated. METHODS AND RESULTS Follow-up data were obtained for 533 patients from 22 institutions at up to 8.7 years after an initial balloon pulmonary valvuloplasty. Patients were grouped based on defined long-term outcomes, and the independent effects of patient selection and technical factors were sought in multivariate statistical analyses. At follow-up, 23% of patients were noted to have an outcome judged to be suboptimal because of either a residual right ventricle to pulmonary artery peak systolic gradient of &gt; or = 36 mm Hg or further treatment of pulmonary stenosis requiring repeat balloon pulmonary valvuloplasty or surgical therapy. Significant independent predictors of a suboptimal long-term outcome included an earlier study year of the initial valvuloplasty (adjusted odds ratio, 0.71 per consecutive year), a small valve hinge point diameter (0.81 per 1-mm increase), and a higher immediate residual gradient (1.32 per 10 mm Hg increase). A smaller ratio of balloon to valve hinge point diameter significantly predicted suboptimal outcomes for patients with valve morphologies classified as typical (0.52 per 0.1 increase in ratio) and complex (primarily postsurgical valvotomy, 0.43) but not for patients with dysplastic (0.95) or combined morphologies (dysplasia with commissural fusion, 1.01). Patient age, the presence of Noonan's syndrome or associated cardiac lesions, pre-balloon valvuloplasty hemodynamic parameters, and the use of a simultaneous double-balloon technique did not independently predict follow-up outcomes. CONCLUSIONS Accurate prognostication after balloon pulmonary valvuloplasty depends on the careful determination of valvar anatomy. The use of an appropriate ratio of balloon to valve hinge point diameter in the setting of typical valve morphology will optimize the chance of long-term success.
Hot Calcaneus on Three-Phase Bone Scan Due to Bone Bruise
Authors: GABRIEL SOUDRY, FINN MANNTING
Journal: Clinical Nuclear Medicine (1995)

A 35-year-old nurse, with no significant medical history and no recollection of foot trauma, was persistently experiencing left heel pain worsened by walking. An ankle and foot plain radiograph showed no abnormality. After 6 months, a three-phase radionuclide bone scan was obtained that showed markedly increased tracer uptake in all three phases in the region of the left calcaneus. An MRI of the left foot showed a “bone bruise” involving the anterior aspect of the calcaneus.
Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: Therapeutic implications
Authors: Anand Mehta, Sandra Carrouée, Bertha Conyers, Robert Jordan, Terry Butters, Raymond A. Dwek, Timothy M. Block
Journal: Hepatology (2001)

Previously we have shown that the imino sugar inhibitor of N–linked glycan processing, N–nonyl–deoxynojirimycin (N–nonyl–DNJ), had antiviral activity in the woodchuck model of chronic hepatitis B virus (HBV) infection. In studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit HBV secretion without inhibiting N–linked glycoprocessing. Although N–nonyl–DNJ is an inhibitor of the endoplasmic reticulum (ER) glucosidase, here it is shown that N–nonyl–DNJ retained antiviral activity at concentrations that had no significant impact on ER glucosidase function. Taken together, these results suggested that N–nonyl–DNJ possessed an antiviral activity attributable to a function other than an impact on glycoprocessing. This hypothesis was confirmed by experiments showing that N–nonyl–deoxygalactojirimycin (N–nonyl–DGJ), an alkyl derivative of galactose with no impact on glycoprocessing, retains anti–HBV activity. The data suggest that N–nonyl–DGJ exerts its antiviral action at a point before viral envelopment and may prevent the proper encapsidation of the HBV pregenomic RNA.
Trypanosoma cruzi. Surface antigens of blood and culture forms.
Authors: N Nogueira, S Chaplan, J D Tydings, J Unkeless, Z Cohn
Journal: The Journal of Experimental Medicine (1981)

The surface polypeptides of both cultured and blood forms of Trypanosoma cruzi were iodinated by the glucose oxidase-lactoperoxidase technique. Blood-form trypomastigotes (BFT) isolated form infected mice displayed a major 90,000-Mr component. In contrast, both epimastigotes and trypomastigotes obtained form acellular cultures expressed a smaller 75,000-Mr peptide. Both major surface components were presumably glycoproteins in terms of their binding to concanavalin A-Sepharose 4B. Within a 3-h period, both blood and culture forms synthesized their respective surface glycoproteins (90,000 Mr and 75,000 Mr, respectively in vitro. [35S]methionine-labeled surface peptides were immunoprecipitated with immune sera of both human and murine origin. A panel of sera form patients with chronic Chagas' disease and hyperimmunized mice recognized similar surface peptides. These immunogens were the same components as the major iodinated species. The major BFT surface peptide was readily removed by trypsin treatment of the parasites, although the procedure did not affect the 75,000-Mr peptide from the culture forms. Two-dimensional polyacrylamide gel electrophoresis revealed that the 90,000-Mr peptide found on BFT was an acidic protein of isoelectric point (pI) 5.0, whereas, the 75,000-Mr peptide form culture-form trypomastigotes has a pI of 7.2. The 90,000-Mr component is thought to be responsible for the anti-phagocytic properties of the BFT (1).
Activation of the p75 Neurotrophin Receptor through Conformational Rearrangement of Disulphide-Linked Receptor Dimers
Authors: Marçal Vilar, Ioannis Charalampopoulos, Rajappa S. Kenchappa, Anastasia Simi, Esra Karaca, Alessandra Reversi, Soyoung Choi, Mark Bothwell, Ismael Mingarro, Wilma J. Friedman, Giampietro Schiavo, Philippe I.H. Bastiaens, Peter J. Verveer, Bruce D. Carter, Carlos F. Ibáñez
Journal: Neuron (2009)
Cholesterol and the Law
Authors: RICHARD N. PODELL
Journal: Circulation (1973)

Diet CholesterolSaturated fatIN 1965 the American Heart Association recom- mended that the public restrict dietary intake of cholesterol and saturated fat.'Recently the AMA Council on Food and Nutrition endorsed a similar policy.2Will Americans be able to accept these recommendations despite a clear preference for foods which are high in cholesterol and saturated fat?3 Perhaps, but only if the foods which are low in cholesterol and saturated fat meet the public's demand for good taste at a reasonable price.Fortunately, we have the technology to produce most of our favorite foods in varieties that are low in cholesterol and saturated fat.4 5 Yet many of these products are not generally available.Why? Food laws and government policy have held back the development and sale of appetizing low cholesterol, low saturated fat food.As a result individuals are forced to choose between foods they enjoy and the often less palatable food their doctor recommends.In effect we have fostered a powerful "procholesterol" national food policy.The effects of this policy on the nation's eating habits are evident in at least four major areas.First, standards for labeling food products have not been imposed.On January 19, 1973, the Food and Drug Administration announced that it will begin to allow the cholesterol and saturated fat content of foods to be printed on their label.
Tobacco and cancer: epidemiology and the laboratory.
Authors: P Vineis, N Caporaso
Journal: Environmental Health Perspectives (1995)

Tobacco smoke contains many mutagenic and carcinogenic chemicals. Both whole tobacco smoke and extracts induce tumors in experimental animals. Work with carcinogen-macromolecule adducts provided evidence for the action of specific chemicals. Molecular epidemiology studies suggested that point mutations in tumor-suppressor genes (e.g., p53) and oncogenes (e.g., ras) may be specific both for the type of tumor and for the critical environmental exposure. The consistency among investigations on oncogene/tumor-suppressor gene mutations in lung cancer (and other tobacco-related cancers) in smokers is highly suggestive, although we still lack information about the time sequence between exposure, gene mutation, and cancer onset. Current work that deserves emphasis includes investigations revealing that lungs of smokers contain benzo[a]pyrene diol-epoxide-guanine DNA adducts, which are in accordance with the type of mutations found in K-ras or p53 genes (G to T transversions). In addition, DNA in human exfoliated bladder cells showed a derivative of 4-aminobiphenyl as a main adduct; there was also an association between smoking habits (amount and type of tobacco) and the levels of both DNA adducts and hemoglobin adducts formed by aromatic amines. Increasing evidence indicates that genetically based metabolic polymorphisms exert a role in modulating individual susceptibility to the action of tobacco carcinogens. Overall, the weight of evidence strongly supports the causal nature of the association between smoking and cancer and falsifies Fisher's hypothesis that the association was due to confounding by genetic predisposition.
Coming to Grips with Foodborne Infection — Peanut Butter, Peppers, and Nationwide Salmonella Outbreaks
Authors: Dennis G. Maki
Journal: New England Journal of Medicine (2009)

In the past year, we have been confronted by two large nationwide outbreaks of salmonella infection. Dr. Dennis Maki explores ways to prevent foodborne infections and argues that it is time to launch a major effort to gain public acceptance of irradiation of high-risk foods.
The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia regardless of JAK2V617F mutational status—clinical correlates in a study of 226 consecutive patients
Authors: A Pardanani, T L Lasho, C M Finke, N Gangat, A P Wolanskyj, C A Hanson, A Tefferi
Journal: Leukemia (2009)
Monitoring of Adverse Drug Events in Hospitals
Authors: Dianne L. Kennedy
Journal: JAMA (1991)

The article appearing in this issue of<i>JAMA</i>by Classen et al,<sup>1</sup>"Computerized Surveillance of Adverse Drug Events in Hospital Patients," emphasizes the importance of adverse drug event (ADE) monitoring in hospitals. The authors' automated system includes rapid computerized identification of potential ADEs, with evaluation by a clinical pharmacist, and is coupled with enhanced hospital staff reporting. Over the 18-month study period, ADE detection and reporting increased 60-fold. The distinctive feature of this program is rapid communication with those providing the patient's medical care. The authors report that "over 75% of verified ADEs in this study did not have the causative agent stopped until study personnel informed the physician of the ongoing ADE."<sup>1</sup> As recognized by the Food and Drug Administration (FDA), the Joint Commission on Accreditation of Healthcare Organizations, and others,<sup>2-4</sup>active hospital surveillance of drug use and resultant ADEs serves many purposes,