tbuckley/cabot-search huggingface dataset:
Is the Critical Reader Dead?
Authors: Alfred Soffer
Journal: JAMA (1967)

The illustrations in a communication which recently appeared in a reputable medical journal looked vaguely familiar to me. A hurried search in our periodical files provided a full explanation for this episode of apparent déjà vu. A truncated version of the report and a few of the identical figures (obviously provided by the senior investigator) had been printed in a medical news magazine several months before. Staffs of journals representing every medical discipline are reporting comparable experiences. Thus, in many instances, the pattern of communication between investigator and clinician has altered dramatically. Intensive efforts to provide a plethora of news reports written exclusively for physicians is a recent phenomenon. Has introduction of mass distribution news periodicals for the physician decreased the importance of traditional medical journals? Are these media truly "competitive," or are the functions they serve so different that the discretionary reader would find it impossible to substitute one
Transient, Marked, Unexplained Elevation of Serum Alkaline Phosphatase
Authors: Peter G. Steinherz
Journal: JAMA (1984)

Five children, aged 16 to 38 months, were found to have serum alkaline phosphatase levels seven to 30 times the upper limit of the reference range. Studies suggested a skeletal origin for the enzyme. No other abnormalities or explanations for the unusual enzyme levels were found. The enzyme levels returned to the reference range. A retrospective review of the records of 74 children with lymphoblastic leukemia, who were 2 to 4 years of age at diagnosis, disclosed only four cases of transient, isolated serum alkaline phosphatase elevation similar in degree to those described herein. The review covered 661 patient-years of follow-up and 2,417 enzyme measurements. Benign, transient hyperphosphatasemia is a rarely recognized clinical entity. Awareness of this condition should curtail the extensive evaluation that may follow the detection of such an abnormality. (<i>JAMA</i>1984;252:3289-3292)
GASTRIC SECRETION AFTER HISTAMINE: SODIUM AND POTASSIUM CONTENT AND PEPSIN ESTIMATION
Authors: J. H. Austin, George D. Gammon
Journal: Journal of Clinical Investigation (1931)

Since Prout (1824) first demonstrated the presence of HC1 in the gastric juice and Beaumont (1833) reported the demonstration by Dunglinson and Emmett of the bases, K, Na, Mg, and Ca, the com- position of the secretion of the stomach has been repeatedly studied.The literature has been reviewed by Rosemann (1920), Carlson (1923), MacLean and Griffiths (1928), Gamble and
Prognostic implications and predictors of enhanced regional wall motion of the noninfarct zone after thrombolysis and angioplasty therapy of acute myocardial infarction. The TAMI Study Groups.
Authors: C L Grines, E J Topol, R M Califf, R S Stack, B S George, D Kereiakes, J M Boswick, E Kline, W W O'Neill
Journal: Circulation (1989)

Although impairment of left ventricular function in acute myocardial infarction is closely related to extent of necrosis, function in the noninfarct zone also contributes to global performance and thus may be of prognostic importance. We evaluated left ventricular regional wall motion by the centerline chord method in 332 patients treated with intravenous tissue-type plasminogen activator (t-PA) in the multicenter Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. All patients had acute contrast ventriculograms of suitable quality for analysis, and 266 patients had paired acute and day 7 ventriculograms. Enhanced function of the noninfarct zone was present during acute catheterization (+0.3 SD/chord) and was associated with preservation of the acute ejection fraction (p = 0.0001). Multiple linear regression analysis revealed the most powerful clinical factor associated with enhanced function of the noninfarct zone was the absence of multivessel disease (p = 0.0001). Clinical factors that were related weakly to noninfarct zone function included female gender (p = 0.08) and higher flow in the infarct artery (p = 0.03). Neither the degree of infarct zone dysfunction nor infarct location was associated with hyperkinesis of the noninfarct zone. In hospital, mortality was closely related to function in the noninfarct zone (p = 0.006), ejection fraction (p = 0.025), and the number of diseased vessels (p = 0.009) but was not related to infarct zone function (p = 0.128).(ABSTRACT TRUNCATED AT 250 WORDS)
Editorial
Authors: Christopher L.R. Barratt, Jackson Kirkman-Brown
Journal: Human Reproduction Update (2005)

Two recent reviews discuss the importance of the female tract in regulating the function of the spermatozoon during its eventful journey to the site of fertilization in this journal. However, our understanding of the nature of this journey, specifically in the human, is remarkably poor. What is also clear is the discourse between what is likely happening in vivo and the design of our experiments in vitro. Our conclusion is that, to date, we have been studying the spermatozoa in the wrong environment, in the wrong way and at the wrong time.
Linear Loss of Insulin Secretory Capacity During the Last Six Months Preceding IDDM: No effect of antiedematous therapy with ketotifen
Authors: Kirsten P Böhmer, Hubert Kolb, Bernd Kuglin, Jürgen Zielasek, Achim Hübinger, Eberhard F Lampeter, Bruno Weber, Victoria Kolb-Bachofen, H U Jastram, Jörg Bertrams, F Arnold Gries
Journal: Diabetes Care (1994)

To investigate the effect of an antiedematous therapy with the histamine antagonist ketotifen on beta-cell function in late prediabetes.In a randomized double-blind placebo-controlled study, ketotifen was administered for 3 months to 9 islet cell antibody positive (ICA+) prediabetic patients with a first-phase insulin response (FPIR) below the 2.5th percentile to preserve residual beta-cell function. Patients were followed by intravenous glucose tolerance tests (IVGTTs) every 4-6 weeks for determination of FPIR, HbA1, ICAs, and insulin autoantibodies. In 5 patients, the immune activation state was followed by determination of serum levels of tumor necrosis factor-alpha (TNF-alpha), beta 2-microglobulin, and C-reactive protein (CRP).Seven of nine patients developed diabetes within one year of follow-up. Irrespective of treatment with ketotifen, a slow and linear decline (P < 0.05) of 1 + 3-min insulin values was observed in sequential IVGTTs in those 7 patients who developed insulin-dependent diabetes mellitus (IDDM) during follow-up. The 2 other patients showed wide fluctuations of the insulin response with a threefold increase of initial insulin levels. HbA1 did not correlate with FPIR. Fasting blood glucose increased significantly during the study (P < 0.05). Individual levels of serum TNF-alpha, CRP, and beta 2-microglobulin did not change during the study.The study could not demonstrate preservation of beta-cell function by ketotifen in the late stage before manifestation of clinical diabetes. Manifestation is preceded in the last 6 months by a steady loss of the FPIR without rapid deterioration immediately before diagnosis and without signs of increased immune activity.
NHS could save 210m a year if all cancers were diagnosed as early as in best areas
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Nearly half of all cancers in England are diagnosed at an advanced stage, when the chances of survival are reduced and treatment is more expensive, an analysis has found.

Although the research from the charity Cancer Research UK found that 83% of breast cancers were diagnosed at stage I or II, the proportion of lung cancers diagnosed at an early stage was just 23%. The proportion of non-Hodgkin’s lymphomas diagnosed at stage I or II was also low, at 32%, while the proportion of ovarian and colorectal cancers identified at these stages was 44% and 45% respectively. Overall the analysis found that 54% of cancers were diagnosed at stages I and II.

There was also wide geographical variation across England in the …
ON A CASE OF SPASMODIC SYRINGOMYELIA
Authors: J. S. Bury
Journal: BMJ (1910)

THERE are few diseases in which the symptoms present so many variations, both in kind and in grouping, as in syringomyelia.The most characteristic features of the disease are: Loss of sensibility to pain and temperature affecting portions of the arms and the upper part of the chest; muscular atrophy resembling in its distribution and progress that of " progressive muscular atrophy," and trophic disturbances of the skin, bones, and joints.Associated with these symptoms there may be loss of tactile sensibility, a spastic weakness of the legs varying much in intensity, ataxia, enlargement of a limb, or signs of implication of some of the cranial nerves,.or of the cervical sympathetic.According to the Dresence or absence of any of these symptoms, to their relative preponderauce and to the variationsj in their combination, the diagnosis in certain cases.may be difficult, and may involve a consideration of disseminate sclerosis, dis-
936 C-MET AND GP130 MEDIATE ANTIBACTERIAL SIGNALLING DURING CHOLESTATIC LIVER INJURY VIA TLR4 AND THE INDUCTION OF THE ACUTE-PHASE RESPONSE
Authors: A. Giebeler, M. Kaldenbach, S. Erschfeld, C. Birchmeier, C. Trautwein, K. Streetz
Journal: Journal of Hepatology (2010)
Abstract PR7: Visualizing the dynamic and heterogeneous responses of single cells to inhibitors of the growth factor signaling network
Authors: John Albeck, Yin P. Hung, Gregory Leya, Gary Yellen, Gordon Mills, Joan Brugge
Journal: Cancer Research (2012)

Abstract The growth factor signaling network, including the Akt, ERK, mTOR and other pathways, is deregulated in many diseases and is a prominent target for therapeutic inhibitors. The effectiveness of these inhibitors is limited by the existence of homeostatic feedback loops that act to restore signaling and attenuate the effects of inhibition. To obtain the single-cell data necessary to fully characterize these rapid and heterogeneous responses, we developed a library of mammary epithelial cells stably expressing over 90 fluorescent protein-based reporters. This library comprises reporters for: cellular processes including cell death, cell cycle, protein translation, and metabolism; kinases including ERK, Akt and AMPK; and microRNAs involved in the regulation of cellular differentiation and stress response. Using high-throughput live-cell microscopy and computational image analysis, we monitored the responses of these pathways to inhibitors of EGFR, ErbB2, PI3K, mTOR, MEK, Raf, and Bcl-2. This analysis revealed unexpectedly dynamic fluctuations in key pathways including ERK, Akt, and glycolysis. In one example, inhibition of EGFR transformed constitutive ERK activity into intermittent bursts of activity ranging in duration from 20-90 minutes with high cell-to-cell variability. Characterization of ERK activity pulses revealed that their frequency depended on the level of EGF receptor activity and that their duration was essential for controlling the commitment to cell proliferation. In sharp contrast, inhibition of MEK altered the amplitude, rather than the frequency, of ERK activity. Using these live-cell measurements in combination with high content immunofluorescence, we constructed a computational model of feedback loops controlling ERK activity pulses. Quantitative mapping of ERK output to proliferation rate revealed a distinct and exquisitely sensitive threshold of ERK output required for proliferation. Potential strategies for reducing ERK output below this threshold and effectively blocking proliferation include dual inhibition of upstream regulators or intermittent high-dose inhibition. Single-cell quantitative analysis of inhibitor responses is now being extended to other pathways to identify signaling dynamics and information transfer properties that enable effective therapeutic targeting of the network. This proffered talk is also presented as Poster A19. Citation Format: John Albeck, Yin P. Hung, Gregory Leya, Gary Yellen, Gordon Mills, Joan Brugge. Visualizing the dynamic and heterogeneous responses of single cells to inhibitors of the growth factor signaling network [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr PR7.
Multiple Autoimmune Diseases after Autologous Stem-Cell Transplantation
Authors: Toshiyuki Bohgaki, Tatsuya Atsumi, Takao Koike
Journal: New England Journal of Medicine (2007)

The authors report on a 19-year-old woman with systemic sclerosis who underwent CD34+-selected autologous hematopoietic stem-cell transplantation in March 2001. The dermal sclerosis improved immediately after transplantation, but thrombocytopenia and Graves' disease developed.
Screening for Genetic Diseases
Authors: Arno G. Motulsky
Journal: New England Journal of Medicine (1997)

With better knowledge of the genetics of various diseases, testing for the underlying defects with the use of biochemical and molecular techniques is increasingly possible. The practical aim of these tests is the prevention and treatment of disease. The first widespread screening test was for the detection of phenylketonuria in newborns. In addition to screening newborns, there are other strategies for identifying genetic disorders. Screening for fetal disease has become common during pregnancy and includes searching for chromosomal defects (such as in Down's syndrome) with amniocentesis or chorionic-villus sampling. Screening of maternal blood for alpha-fetoprotein to detect neural-tube defects and . . .
The Effects of Triglyceride Absorption upon Glucagon, Insulin, and Gut Glucagon-Like Immunoreactivity
Authors: Ingolf Böttger, Richard Dobbs, Gerald R. Faloona, Roger H. Unger
Journal: Journal of Clinical Investigation (1973)

The effects of a fat meal upon plasma insulin, glucagon, and glucagon-like immunoreactivity (GLI) have been studied in conscious dogs and in human volunteers. In dogs the intraduodenal instillation of 10 g/kg of peanut oil was accompanied by increases in the mean plasma levels of all three polypeptides that averaged 5 μU/ml, 107 pg/ml, and 2.1 ng/ml, respectively. 3 g/kg of peanut oil, when emulsified with egg yolk, elicited a much greater response of the three hormones, and a physiologic dose of 1 g/kg in emulsified form also caused a significant rise in glucagon and GLI. The islet cell hormone response was not ascribable to chylomicronemia since intravenous infusion of canine chyle failed to stimulate glucagon secretion; moreover, in dogs with a thoracic duct fistula in which chyle was excluded from the circulation, the intraduodenal administration of a fat meal elicited the normal islet cell hormone response, as well as a rise in GLI. 10 g/kg of medium-chain triglycerides failed to elicit these same responses. In six human volunteers the oral administration of 3 g/kg peanut oil was accompanied by increments of 2 μU/ml, 26 pg/ml, and 1.5 ng/ml in the mean levels of insulin, glucagon, and GLI. The changes in insulin and glucagon in man were neither statistically significant nor biologically impressive.
Glucose-Insulin-Potassium Reduces the Incidence of Low Cardiac Output Episodes After Aortic Valve Replacement for Aortic Stenosis in Patients With Left Ventricular Hypertrophy
Authors: Neil J. Howell, Houman Ashrafian, Nigel E. Drury, Aaron M. Ranasinghe, Hussain Contractor, Henrik Isackson, Melanie Calvert, Lynne K. Williams, Nick Freemantle, David W. Quinn, David Green, Michael Frenneaux, Robert S. Bonser, Jorge G. Mascaro, Timothy R. Graham, Stephen J. Rooney, Ian C. Wilson, Domenico Pagano
Journal: Circulation (2011)

Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery.Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands.Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.
Schizophrenia and Hormones
Authors: William Malamud
Journal: New England Journal of Medicine (1951)

ONE of the most impressive phenomena observed during a recently completed survey1 of research activities in schizophrenia was the widespread interest in steroid chemistry and adrenocortical function in their application to both clinical and investigative work in this disease. The immediate cause of this interest was obviously the fact that adequate amounts of an adrenocortical hormone (cortisone or Compound E) and adrenocorticotrophic hormone (ACTH) were made available, and had been successfully applied in the treatment of arthritis.2 , 3 The almost miraculous results reported after the use of cortisone and ACTH in arthritis, combined with the psychological effects produced by these substances . . .
Positive predictive value is poor in low risk populations seen in universal screening for HIV infection
Authors: J. R. Greig, D. Batchelor, M. Wallis
Journal: BMJ (2013)

Sugarman does not mention an inherent problem with screening for disease in low risk populations1—the poor positive predictive value (PPV) of even the most specific tests. The PPV conveys the likelihood that a positive test result is correct. It is related to test specificity but can be highly dependant on disease prevalence. Suggested screening thresholds range from one case per 500 …
IV. On the Biology of Creativity
Authors: Hudson Hoagland
Journal: JAMA (1965)

I would like to comment on some biologic aspects of creativity. The higher forms of animals, including ourselves, have been extensively studied by behavioral psychologists from the point of view of their drives and motivations. In recent years, it has been discovered that one fundamental motivation for animal behavior seems to be curiosity—the drive to explore without reference to any particular end in view of food or reward. This is a biologic characteristic of animals ranging from cockroaches to man. For example, Robert Butler found that monkeys enclosed in a dimly lighted box would press a lever to open an opaque window for a few seconds. The window then closed automatically and could be opened again only by pressing a lever. A monkey would open and reopen the window for hours on end for no reward other than an opportunity to look out and see what was on the other
The Medical Response to Nuclear War
Authors: Sidney Alexander
Journal: JAMA (1985)

To the Editor.—  Your Aug 2 issue, which commemorates the 40th anniversary of the Hiroshima bombing, was superb. In particular, Paul Boyer's article was a gem. It should be required reading for all physicians interested in these important issues.  American Medical Association is to be congratulated for recognizing that the medical consequences of nuclear war, the psychologic factors that fuel the arms race, and diversion of funding from medical care to nuclear weapons research, development, and production are all properly within the professional interest and responsibility of physicians.  I would like to comment on some of the points made by Day and Waitzkin 1 in their article, The Medical Profession and Nuclear War. Their statement that the US leaders of the International Physicians for Prevention of Nuclear War (all of whom are also members of Physicians for Social Responsibility [PSR]) blame the United States chiefly for the arms race is
Journal of Chronic Fatigue Syndrome: Multidisciplinary Innovations in Research, Theory and Clinical Practice
Authors: Josephine L. Dorsch
Journal: JAMA (1997)

<i>Journal of Chronic Fatigue Syndrome</i>provides a forum for presenting integrated, multidisciplinary studies regarding chronic fatigue syndrome (CFS). In its inaugural issue, the coeditors express ambivalence about the need for a journal dedicated to CFS but conclude that a specialty journal affords advantages to the field by reviewing a widely scattered literature, enhancing the credibility of the work in the field, and increasing research in CFS and related areas. The journal attempts to blend scientific data in the form of original research with opinions and hypotheses regarding etiology and treatment of CFS. Each issue consists of editorials, original research, reviews, special features, and a "Literature in Review" section. Members of the international editorial board are recognized for their work in this field; they represent four countries and diverse disciplines. The journal's instructions for authors clearly state that all submissions will be regorously peer-reviewed by members of the editorial board and possibly by other specially qualified individuals. As sometimes happens with new journals, however, many of the articles are by editorial board members.
Alcohol, Drugs, and Traffic Safety
Authors: Lee N. Hames
Journal: JAMA (1976)

It is impossible in brief compass to adequately review a book of more than 900 pages, containing 93 papers on such varied topics as "Effects of Alcohol on Visual Accommodation and Eye Movement Latency," "Immunoassays for the Detection of Drugs in Drivers," and "Seven Years Experience of Blood-Alcohol Limits in Britain." At best, one might try to identify some unifying trends or philosophies. The very first paper, appropriately addressed to epidemiologic issues, was given by Julian A. Waller, MD, who has done so much in identifying methodologic errors and careless research in this field. Other papers echo Waller's plea for better epidemiologic studies and for the need to set priorities in dealing with the problem of alcohol and other drugs. A number of communications cover pharmacological, physiological, and psychological aspects, particularly the hazardous effects of low and moderate levels of alcohol on the driving performance of certain persons, as well