tbuckley/cabot-search huggingface dataset:
Selective Coronary Arteriography
Authors: Walt F. Weaver
Journal: JAMA (1976)

Over a 33-month period, selective coronary arteriography was performed in 627 consecutive patients in a 385-bed, non-university-affiliated community hospital. Mortality was 0.16% (one death); there was also one nonfatal myocardial infarction. No deaths or myocardial infarctions occurred in the last 369 consecutive patients in this series when routine systemic heparinization was introduced. Substantially greater risk of mortality (2.6%) and nonfatal myocardial infarction (2.6%) was encountered in an earlier series of 78 consecutive patients for whom a different protocol was used. It included extensive exercise hemodynamic studies with the use of percutaneous arterial angiographic catheters, without systemic heparinization. This indicates that coronary arteriography can be carried out with acceptable risk in a community hospital. Protocols should be designed to minimize the time that catheters are in the arterial system. Systemic heparinization may reduce the risk of procedure-related death and myocardial infarction.
Impact of smoking on mortality and life expectancy in Japanese smokers: a prospective cohort study
Authors: R. Sakata, P. McGale, E. J. Grant, K. Ozasa, R. Peto, S. C. Darby
Journal: BMJ (2012)

<b>Objective</b> To investigate the impact of smoking on overall mortality and life expectancy in a large Japanese population, including some who smoked throughout adult life. <b>Design</b> The Life Span Study, a population-based prospective study, initiated in 1950. <b>Setting</b> Hiroshima and Nagasaki, Japan. <b>Participants</b> Smoking status for 27 311 men and 40 662 women was obtained during 1963-92. Mortality from one year after first ascertainment of smoking status until 1 January 2008 has been analysed. <b>Main outcome measures</b> Mortality from all causes in current, former, and never smokers. <b>Results</b> Smokers born in later decades tended to smoke more cigarettes per day than those born earlier, and to have started smoking at a younger age. Among those born during 1920-45 (median 1933) and who started smoking before age 20 years, men smoked on average 23 cigarettes/day, while women smoked 17 cigarettes/day, and, for those who continued smoking, overall mortality was more than doubled in both sexes (rate ratios versus never smokers: men 2.21 (95% confidence interval 1.97 to 2.48), women 2.61 (1.98 to 3.44)) and life expectancy was reduced by almost a decade (8 years for men, 10 years for women). Those who stopped smoking before age 35 avoided almost all of the excess risk among continuing smokers, while those who stopped smoking before age 45 avoided most of it. <b>Conclusions</b> The lower smoking related hazards reported previously in Japan may have been due to earlier birth cohorts starting to smoke when older and smoking fewer cigarettes per day. In Japan, as elsewhere, those who start smoking in early adult life and continue smoking lose on average about a decade of life. Much of the risk can, however, be avoided by giving up smoking before age 35, and preferably well before age 35.
Abstract 4953: Identification of direct target engagement biomarkers for kinase drug discovery using quantitative mass spectrometry: PDK1 case study
Authors: Jannik N. Andersen, Cloud P. Paweletz, Roy Pollock, Kumiko Nagashima, Alan Northrup, Hendrickson C. Ronald, An Chi
Journal: Cancer Research (2010)

Abstract The human genome encodes some 500 protein kinases and an estimated twenty percent of drugs currently in development target this enzyme class. Because kinase inhibitors frequently bind to the conserved ATP-binding pocket, in vitro kinase selectivity profiling of drug candidates are an integral part of the small-molecule drug discovery process. Likewise, the co-development of pharmacodynamic (PD) biomarkers is critical to drug development as they link drug-target inhibition in cells with biological activity. As such PD biomarkers are essential for the interpretation of in vivo PK/PD/efficacy studies, which ultimately inform medicinal chemistry. Here, we present a universal mass-spectrometry-based approached to discover kinase drug-target engagement biomarkers using the phosphoinositide dependent protein kinase 1 (PDK1) as an example. Western blot analysis using a commercial available phosphosite-specific PDK1 antibody (Ser241) revealed that classical, ATP-competitive PDK1 inhibitors do not dynamically impact PDK1 T-loop phosphorylation in cells, despite cell biochemical inhibition of phospho-AKT(Thr308), a bona fide PDK1 substrate phosphorylation site. However, because receptor tyrosine kinases (RTKs), lipid kinases and other pathways often signal via AKT, the monitoring of phospho-AKT as a PD biomarker for PDK1 is not sufficient for delineating the specificity of small-molecule inhibitors and ascertain the degree of PDK1 target engagement in cells. Here, we used stable isotope labeling by amino acids (SILAC) in cell culture combined with immunoprecipitation of PDK1 protein from cells for quantitative mass-spectrometry-based identification of phosphorylation sites modulated by PDK1 inhibitor treatment. We mapped 10 Serine/Threonine phosphorylation sites on PDK1 including several novel phosphorylation sites. Of these, two PDK1 phosphorylation sites (Ser410 and Thr513) were modulated by pharmacological PDK1 inhibition and the degree of dephosphorylation correlated with inhibitor potency in PDK1 enzymatic assays. By contrast, pharmacological inhibition of PDK1 did not quantitatively modulate PDK1 T-loop phosphorylation (Ser241) consistent with the initial western blot analysis. Altogether, our study provides proof-of-concept for identifying novel kinase target engagement PD biomarkers for PDK1, complementing pathway biomarkers such p-AKT and p-S6RP, which are modulated broadly by PI3K-pathway targeting agents including inhibitors of PI3K/mTOR and RTKs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4953.
Calmodulin Mediates Calcium-Dependent Inactivation of the Cerebellar Type 1 Inositol 1,4,5-Trisphosphate Receptor
Authors: Takayuki Michikawa, Junji Hirota, Seiko Kawano, Masayasu Hiraoka, Maki Yamada, Teiichi Furuichi, Katsuhiko Mikoshiba
Journal: Neuron (1999)
Histological Quality of Polyps Resected Using the Cold Versus Hot Biopsy Technique
Authors: K. Mönkemüller, L. Fry, B. Jones, C. Wells, I. Mikolaenko, M. Eloubeidi
Journal: Endoscopy (2004)

Background and Study Aims: The monopolar hot biopsy technique is a widespread method of removing and cauterizing small colonic polyps. Due to the insulated cups of the biopsy forceps, it also allows adequate histological interpretation of the resected specimen. In our experience, polyps removed using the monopolar hot biopsy technique have been less histologically interpretable in comparison with polyps removed using cold biopsy forceps. The aim of this study was to assess and compare the diagnostic quality of polyps obtained using the hot biopsy and cold biopsy techniques. Patients and Methods: This was a prospective study of consecutive patients undergoing colonoscopy with removal of polyps using either hot biopsy or cold biopsy techniques. One experienced endoscopist using the same techniques carried out the biopsies. An experienced gastrointestinal pathologist, blinded to the technique used, evaluated the specimens for diameter, artifacts, cautery damage, tissue fragmentation, and general histological and diagnostic quality. Statistical analysis was carried out using the chi-squared test, Fisher’s exact test, and Student’s t-test. Results: Forty-three consecutive patients (84 % men; mean age 63.8 ± 15 years) underwent 88 biopsies (45 hot biopsies and 43 cold biopsies). There were no statistically significant differences between the two study groups with regard to demographic data, indications for colonoscopy, endoscopic findings, or polyp size. Cautery damage, architectural distortion, and tissue fragmentation occurred more frequently in polyps resected using the hot biopsy technique (P < 0.001). Conclusions: The quality of the specimens removed by cold biopsy was generally better than when using hot biopsy technique. Histological evaluation is more difficult in polyps resected with the hot biopsy technique in comparison with the cold biopsy technique. When the nature of polyps affects the patient’s management, a biopsy may be obtained before polyp coagulation.
Delayed Effects of the Military Draft on Mortality
Authors: Norman Hearst, Thomas B. Newman, Stephen B. Hulley
Journal: New England Journal of Medicine (1986)

To study the effect of military service during the Vietnam era on subsequent mortality, we analyzed a randomized natural experiment, the military draft lottery of 1970 to 1972. Between 1974 and 1983, there were 14,145 deaths among California and Pennsylvania men whose dates of birth were in the years for which the draft lottery was held. The group of men with birth dates that made them eligible for the draft had a higher mortality rate than the group with birth dates that exempted them from the draft: suicide was increased by 13 percent (P = 0.005 by two-tailed test), death from motor-vehicle accidents by 8 percent (P = 0.03), and total mortality by 4 percent (P = 0.03). Only 26 percent of the men who were eligible for the draft actually entered the military. If military service (rather than draft eligibility) was the actual risk factor, suicide and death from motor-vehicle accidents would have to have been increased by 86 percent and 53 percent among men who served in the military, to produce the increased risk that we observed among all draft-eligible men. A separate analysis that compared the causes of death in veterans and nonveterans yielded similar estimates: veterans were 65 percent and 49 percent more likely to die from suicide and motor-vehicle accidents, respectively. We conclude that the most likely explanation for these findings is that military service during the Vietnam War caused an increase in subsequent deaths from suicide and motor-vehicle accidents.
Interdisciplinarity: History, Theory, and Practice
Authors: Sheldon Berrol
Journal: JAMA (1992)

Medicine has evolved from the undertaking of the individual practitioner to a state in which many disciplines become involved in administering both diagnostic and treatment services. It has become a standard of care in hospital and clinic-based practice to utilize a multidisciplinary approach to medical care. Multidisciplinary modes of practice, however, do not ensure that participants interact cooperatively, or with the exclusive purpose of patient benefit. The usual mode of interaction within medical academic and clinical environments promotes individualism, protectionism, and some degree of isolation, not infrequently to the detriment of patient care. The stated purpose of this book is to provide a synthesis of theories and methodologies that promote a growing permeability of boundaries and that allow for intellectual accommodation. Health care professionals have been turning to interdisciplinary intervention approaches for several reasons, but the most compelling in medicine is the need to solve problems that are beyond the
Psychiatry: Essentials of Clinical Practice, With Examination Questions, Answers, and Comments
Authors: John M. Craig
Journal: JAMA (1984)

Gregory and Smeltzer with their five contributors have produced a book aptly described by its title. It developed from a "personalized study program for Ohio State Medical Students" that included eight assignments of reading material supplemented with individual meetings with a tutor after each assignment, optional lectures, and a written quiz. This program resulted in high scores in psychiatry on the National Board Examinations above the students' other subjects and above the national average. The authors' approach to the subject follows the medical model and the classification of the disorders follows the<i>DSM-III</i>very closely; indeed some of the descriptions parallel those in the manual. The sequence of chapters reflects the authors' stance in the 15th chapter, when only after discussions of development, evaluation, psychological testing, psychosocial determinants of behavior, community psychiatry, mental retardation, psychiatry and the law, and other matters are problems of schizophrenia and the affective disorders presented.
1286 PRIMARY SCLEROSING CHOLANGITIS IS ASSOCIATED WITH PANCOLITIS AND NOT BACKWASH ILEITIS
Authors: K. Boonstra, K.J. van Erpecum, C.M.J. van Nieuwkerk, J.P.H. Drenth, A.C. Poen, B.J.M. Witteman, H.A.R.E. Tuynman, U.H.W. Beuers, C.Y. Ponsioen
Journal: Journal of Hepatology (2011)
Effect of Preventive Supplementation on Young Children in Niger
Authors: Dominique Roberfroid
Journal: JAMA (2009)

Effect of Preventive Supplementation on Young Children in NigerTo the Editor: In their randomized controlled trial, Ms Isanaka and colleagues 1 found that providing children younger than 5 years with ready-to-use therapeutic food during periods of food insecurity can prevent cases of malnutrition.However, their study presents 2 important methodological difficulties.First, the authors used different reference distributions to define malnutrition at inclusion in the study (National Center for Health Statistics/World Health Organization [NCHS/ WHO], 1978) and at inclusion in the analysis (WHO Child Growth Standards, 2006).A proportion of participants were thus excluded from the analysis on the grounds that they were already malnourished at recruitment according to the WHO reference. 2This proportion was likely substantial and would be expected to consist mainly of children younger than 24 months because the 2 references yield different diagnoses principally in that age range. 2 Unfortunately, this age range has the highest risk of malnutrition. 3This compromises the internal validity of the study, and extrapolation of results to children aged 6 to 60 months requires caution.The problem could be amplified by the interaction of the intervention with child age at baseline (P=.07), a result not fully discussed by the authors.Second, the authors chose purposively a small number of villages that experienced a high prevalence of wasting during the 2005 food crisis.This crisis was an extreme manifestation of a long-term problem, including weak markets, land degradation, and poor access to health services. 4As a result, the study villages were likely to differ from other villages by a number of key characteristics, putting the external validity of the study in question.In addition, it indicates that without addressing the causal complexity of malnutrition any intervention will have limited impact on malnutrition.The intervention in the study by Isanaka et al reduced the rate of wasting by only 36%.
Mutations in Mouse Myeloma Cells: Implications for Human Multiple Myeloma and the Production of Immunoglobulins
Authors: Stephen Weitzman, David H. Margulies, Matthew D. Scharff
Journal: Annals of Internal Medicine (1976)

Multiple myeloma raises a number of puzzling questions about the production of immunoglobulins and the malignant transformation of lymphoid cells. Some of these questions can be approached by studying mouse plasmacytomas and by genetic and biochemical studies of mouse myeloma cells in culture. The synthesis, assembly, glycosylation, and secretion of immunoglobulin has been analyzed in detail using the mouse myeloma system. The development of a technique that detects variants in clones of cultured mouse myeloma cells has led to the demonstration of a unique genetic instability in these cells. Based on these results a model is presented to explain the high frequency of light-chain producing (Bence Jones) myelomas in patients. Finally, mutant cell lines have been recovered which produce defective immunoglobulins similar to those found in heavy-chain disease and some other lymphoproliferative disorders.
Qualitative thesis explored social dislocation and health
Authors: E. Philipp
Journal: BMJ (1995)

EDITOR,--Roland Petchey discusses J S Collings's report on general practice in England in 1950.1 In 1939, a decade before Collings's survey, I wrote my MD thesis on the conditions of the lives of the working population in a new district in relation to health. It was a qualitative and in depth thesis that used statistics as only a supporting framework, and it criticised the lack of attention paid to medical social problems by primary care doctors.

I had started in practice in …
An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML
Authors: Lars Bullinger, Konstanze Döhner, Raphael Kranz, Christoph Stirner, Stefan Fröhling, Claudia Scholl, Young H. Kim, Richard F. Schlenk, Robert Tibshirani, Hartmut Döhner, Jonathan R. Pollack
Journal: Blood (2008)
Child-resistant containers a 'must' in drug-dispensing
Authors: Phil Gunby
Journal: JAMA (1982)

Physicians who dispense pharmaceuticals must use child-resistant containers except when patients such as the elderly or handicapped would be unable to open them, according to the US Consumer Product Safety Commission. The commission monitors compliance with the federal Poison Prevention Packaging Act, and many states have parallel statutes. However, says David Schmeltzer, associate executive director of the commission's Directorate for Compliance and Administrative Litigation, the agency is concerned that some physicians who dispense pharmaceuticals themselves may not understand that they are subject to the law's packaging standards "in the same manner [as for] prescription drugs dispensed by pharmacists." The law provides that non-child-resistant packaging may be provided at a patient's request or a prescribing physician's direction, Schmeltzer concedes. But he emphasizes that this clearly "is to be the exception rather than the rule." Although children's accidental ingestions of aspirin and potentially poisonous substances of all kinds have declined by an
PRESERVATION OF WHITE CELL SOLUTIONS
Authors: Max Trumper
Journal: JAMA (1926)

<h3>To the Editor:</h3> —No doubt it is a common annoying experience for physicians to find their white cell solutions on standing contaminated with molds and especially yeasts. It has been experimentally proved that gentian violet even in high dilutions possesses the power of checking the reproductive mechanism of bacteria. I have applied this by adding one or two drops of gentian violet to the white cell solution (150 cc. of 0.5 per cent acetic acid) and have found no contaminating yeasts or molds after standing for a few months at room temperature.
Reduced-intensity allogeneic transplantation combined with imatinib mesylate for chronic myeloid leukemia in first chronic phase
Authors: Y Luo, X-Y Lai, Y-M Tan, J-M Shi, Y-M Zhao, X-Y Han, G-F Zheng, X-L Zhu, J Sun, Y-L Zheng, G-Q Wu, J-S He, S-Y Chen, A-Y Jin, W-Z Xie, X-J Ye, Z Cai, M-F Lin, H Huang
Journal: Leukemia (2009)
Effect of a mucoactive compound (CO 1408) on airway hyperreactivity and inflammation induced by passive cigarette smoke exposure in guinea-pigs
Authors: A Hernandez, L Daffonchio, L Brandolini, G Zuccari
Journal: European Respiratory Journal (1994)

Environmental exposure to tobacco smoke contributes to the onset of several lung diseases, e.g. chronic bronchitis and asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound, CO 1408, on airway hyperreactivity and lung inflammation induced in guinea-pigs by passive cigarette smoke exposure. Animals were exposed to cigarette smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to histamine was assessed ex-vivo in lung parenchymal strips. As a measure of lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections. Passive smoke exposure potentiated histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment with oral CO 1408 at 400 mg.kg-1 but not 100 mg.kg-1, completely prevented the cigarette smoke-induced airway hyperreactivity. 400 mg.kg-1 CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of CO 1408 to modulate smoke-induced airway hyperreactivity and, to some extent, lung inflammation, an effect which might be of value in the therapy of obstructive pulmonary diseases.
Bariatric Surgery Continues to Show Benefits for Patients With Diabetes
Authors: Mike Mitka
Journal: JAMA (2012)

cessful,” Freischlag said. “That’s a culture shift.” Velazquez also cited the need for more flexibility on the academic tracks toward tenure. Davis and colleagues suggested thatpart-timeappointmentsoradjustments to the time requirements for achieving tenure may also be helpful. Turner and Velazquez agreed that with women making up half of US medical graduates, surgical programs must work harder to attract the best and brightest. “We can’t afford to frighten away a willing and well-qualified candidate as a result of something we could have improved,” Turner said.
Intranasal midazolam for treating febrile seizures in children
Authors: T. Johnson
Journal: BMJ (2001)

EDITOR—The importance of the study by Lahat et al1 is acknowledged both in the editorial by Koren2 and in subsequent correspondence, which recognises the need for effective and safe treatment for acute seizures in the community. But important methodological and analytical issues need to be clarified before the conclusions can be accepted.

The logistics of randomisation are not described in detail, although, firstly, apparently parents were asked to sign a consent form for enrolment in the study after seizures were controlled. The usual ethical practice in randomised controlled trials is to seek consent to randomisation before treatment; here, the order seems to have been reversed unless the controlled seizure actually preceded the seizure for which randomised treatment was allocated. Secondly, randomisation was apparently performed in advance, although this could refer to the frequent practice of drawing up a sequence of treatment allocations before the start of the trial, or it could mean in advance of the trial seizure itself, in which case we would need to know how far in advance. Thirdly, although 100 episodes of febrile seizure were randomly assigned to the two treatments, the analysis is confined to just 52. Under the principle of intention to treat, Lahat et al should report the outcome for all randomised patients' seizures and include them in their primary analysis. It is vital to know exactly what happened to the 48 randomly assigned episodes that are not mentioned further.

Lahat et al conclude that the drugs were equally effective at stopping seizures. This conclusion is drawn from the observation that out of 26 seizures treated with intravenous diazepam 24 responded, compared with 23 out of 26 treated with nasal midazolam; the difference between the percentages is small, at 3.8%. The 95% confidence interval, however, for this difference (diazepam minus midazolam) …