tbuckley/cabot-search huggingface dataset:
A FURTHER STUDY OF PSEUDO, OR MODIFIED SMALLPOX (?)
Authors: T. J. HAPPEL
Journal: JAMA (1901)

At Atlantic City one year ago I reported my experi- ence with 300 cases of pseudo, or modified smallpox (?)This report was made from a personal, bedside study of these cases in all stages of this disease.I presented statistics showing that in some cases not one of the family escaped; in others, only one or two members of a large family showed any signs of the disease; and in others but one case in a large family, even though the members of the family came in daily contact with the disease.It was further shown that the disease lacked many of the distinctive features of true smallpox.Of the 300 cases seen by me, the ordinary fever, or the fever of invasion, was, in a large majority of cases, slight;
Seat-belt Injuries
Authors: J. B. Hamilton
Journal: BMJ (1968)

The drivers and passengers of two cars which collided head-on all wore lap and diagonal seat-belts. Three of the four suffered ruptured viscera and two incurred flexion-compression fractures of the neck. A victim of a traffic accident who was wearing a seat-belt and who has superficial bruising or pain presents a difficult diagnostic problem. Visceral injury should be suspected in such cases.
The Future General Internist
Authors: William C. Steinman
Journal: Annals of Internal Medicine (1995)

Letters15 July 1995The Future General InternistWilliam C. Steinman and Marc J. KahnWilliam C. SteinmanSearch for more papers by this author and Marc J. KahnSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-2-199507150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We disagree with the emphasis and the roles defined for the general internist in the college's recent position paper [1]. The proposal omits the most important role for which general internists should be trained, that of internal medicine specialists. Such physicians know the breadth and depth of internal medicine but do not have the training or competencies to perform the complicated procedures of subspecialists. Recently, there has been a drift away from these masters of the practice of internal medicine to generalists at one extreme and subspecialized subspecialists at the other. To say that “imaging techniques and ...REFERENCE1. American College of Physicians. The role of the future general internist defined. Ann Intern Med. 1994; 121:616-22. Google Scholar Author, Article, and Disclosure InformationAuthors: William C. Steinman; Marc J. Kahn PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1995Volume 123, Issue 2 Page: 156-158 Keywords Decision making Diagnostic medicine Forecasting Imaging techniques Inpatients Sub-specialty care ePublished: 15 August 2000 Issue Published: 15 July 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE INCREASE OF INSANITY AND TUBERCULOSIS IN THE SOUTHERN NEGRO SINCE 1860, AND ITS ALLIANCE, AND SOME OF THE SUPPOSED CAUSES.
Authors: THEOPHILUS O. POWELL
Journal: JAMA (1896)

The negroes of Georgia, and I might say of the Southern States, up to 1860 enjoyed remarkable mental and physical health, and they were almost entirely exempt from certain diseases to which they are now not only very susceptible, but are dying much more rapidly from these maladies than the whites; namely, insanity and consumption. While they may indicate much less susceptibility to miasmatic fevers, they are becoming more and more susceptible to them every year, and when we consider that heredity is one of the leading factors in the causation of insanity with the whites, and know that twenty-five or thirty years ago insanity and consumption in the negro could not have been attributed to hereditary predisposition save in a very few cases; couple this phenomenal increase in this race since 1860 with the inherited tendencies to these maladies, which we might say is just beginning to be manifested
Intractable angina pectoris. Combined therapy with propranolol and permanent pervenous pacemaker
Authors: V. Warren
Journal: JAMA (1976)

ANGINA pectoris is a manifestation of myocardial hypoxia<sup>1</sup>caused by an imbalance between myocardial oxygen demand and available oxygen supply. In some patients, increased sympathetic tone and heart rate cause oxygen-wasting and provoke recurrent attacks of anginal chest pains at lower levels of physical activity.<sup>2-3</sup>Selective blockade of excessive cardiac sympathetic responses by specific β-adrenergic receptor blocking agents, eg, propranolol hydrochloride, has been shown to reduce the frequency and severity of ischemic chest pains and to increase the effort tolerance in these patients.<sup>4-6</sup>Unfortunately, the higher dose of propranolol required to control the symptoms of angina pectoris in some of these patients may lead to severe symptomatic bradycardia.<sup>7</sup>Three such patients (Table) were treated with propranolol and the use of a permanent pervenous pacemaker (rate, 60 beats per minute), with good control of anginal pains. <h3>Comment</h3> Several advantages derive from the combined use of a pervenous
Severe pulmonary hypertension in patients with severe aortic valve stenosis: clinical profile and prognostic implications
Authors: Joseph F Malouf, Maurice Enriquez-Sarano, Patricia A Pellikka, Jae K Oh, Kent R Bailey, Krishnaswamy Chandrasekaran, Charles J Mullany, A.Jamil Tajik
Journal: Journal of the American College of Cardiology (2002)
Increased glutamine catabolism mediates bone anabolism in response to WNT signaling
Authors: Courtney M. Karner, Emel Esen, Adewole L. Okunade, Bruce W. Patterson, Fanxin Long
Journal: Journal of Clinical Investigation (2014)

WNT signaling stimulates bone formation by increasing both the number of osteoblasts and their protein-synthesis activity. It is not clear how WNT augments the capacity of osteoblast progenitors to meet the increased energetic and synthetic needs associated with mature osteoblasts. Here, in cultured osteoblast progenitors, we determined that WNT stimulates glutamine catabolism through the tricarboxylic acid (TCA) cycle and consequently lowers intracellular glutamine levels. The WNT-induced reduction of glutamine concentration triggered a general control nonderepressible 2-mediated (GCN2-mediated) integrated stress response (ISR) that stimulated expression of genes responsible for amino acid supply, transfer RNA (tRNA) aminoacylation, and protein folding. WNT-induced glutamine catabolism and ISR were β-catenin independent, but required mammalian target of rapamycin complex 1 (mTORC1) activation. In a hyperactive WNT signaling mouse model of human osteosclerosis, inhibition of glutamine catabolism or Gcn2 deletion suppressed excessive bone formation. Together, our data indicate that glutamine is both an energy source and a protein-translation rheostat that is responsive to WNT and suggest that manipulation of the glutamine/GCN2 signaling axis may provide a valuable approach for normalizing deranged protein anabolism associated with human diseases.
A Contribution to the Study of the Pituitary Body
Authors: W. A. Osborne, S. Vincent
Journal: BMJ (1900)

THE PITUITARY BODY.[MARCH 3, 1900w the filter were washed off into a quantity of sterilised water, equal in amount to the broth of the culture taken.The suspension was heated at 60O C. for thirty minutes.Rabbits were inoculated as follows: No. Weight.I 1,750 grams inoculated with 3 c.cm. filtrate. 2II0.. .1,5 IV 11 1 3 it 3 .
Abstract 1503: Rapid detection of somatic mutations in cancer genes
Authors: Michael J. Powell, Larry Pastor, Rachel Diaz, Lily Chen, George Wu, Claudia Li, Aiguo Zhang
Journal: Cancer Research (2014)

Abstract In the context of personalized cancer treatment, tumor mutational analysis by DNA sequencing has been described frequently as the “gold standard”, yet DNA sequencing is one of the least sensitive methods for characterizing mutation. At least 10-20% of a DNA population must be mutant for the mutation to be detected by standard DNA sequencing. Implicit acceptance that this level of sensitivity is sufficient to characterize tumor mutations only makes sense if one assumes that tumors are monoclonal and that all the critical driver mutations will be present in the bulk of the tumor. Yet these are incorrect assumptions. In fact, it has become clear that most if not all colon tumors are polyclonal and heterogeneous. Consequently, tumor driver mutations may not be detectable using standard DNA sequencing methods. In order to rapidly detect these low frequency mutations in tumor derived DNA we have developed a new technology that allows the detection of tumor driver and drug resistance somatic mutations at &amp;lt;0.1% sensitivity using quantitative PCR (qPCR) without the need for digital PCR or droplet digital PCR (ddPCR) methodology. We utilize xeno-nucleic acid (XNA) clamping probes that are specific for the target gene wild-type template and allow only the selective amplification of mismatched mutant templates. Direct detection of driver and drug resistance mutations within 2 hours of obtaining samples in KRAS, NRAS, BRAF, EGFR and JAK2 utilizing real-time qPCR with interchelating fluorescence dye detection. As well as a new end-point post-PCR microtiterplate based target gene mutant amplicon capture format that utilizes colorimetric or chemiluminescence detection will be described. Citation Format: Michael J. Powell, Larry Pastor, Rachel Diaz, Lily Chen, George Wu, Claudia Li, Aiguo Zhang. Rapid detection of somatic mutations in cancer genes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1503. doi:10.1158/1538-7445.AM2014-1503
Effects of lignocaine on intramyocardial conduction in nonischaemic and ischaemic canine myocardium
Authors: R. LEVITES, J. I. HAFT, D. VENKATACHALAPATHY
Journal: Cardiovascular Research (1976)

The effect of lignocaine (USP: lidocaine) on intramyocardial conduction in ischaemic and nonischaemic areas of the left ventricular myocardium was determined in 11 mongrel dogs. Intramyocardial conduction times were assessed during control conditions, 15 min after coronary ligation, and following lignocaine administration. Coronary occlusion resulted in a disparity between the conduction velocities in the ischaemic and nonischaemic zones. Ater lignocaine administration conduction to the ischaemic area was further decreased. However, conduction to the nonischaemic area was decreased to a relatively greater extent, resulting in a significant decrease in the disparity of conduction velocities in the two areas. It is concluded (1) that lignocaine exerts dissimilar quantitative effects on the nonischaemic and acutely ischaemic myocardium and (2) that these differential effects decrease the inhomogeneity of intraventricular conduction. It is possible that this action may play a role in the suppression of re-entrant arrhythmias.
Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays.
Authors: D E Symer, R Z Dintzis, D J Diamond, H M Dintzis
Journal: The Journal of Experimental Medicine (1992)

We present evidence that direct T cell receptor (TCR) occupancy by antigen can either activate or inhibit T cells, depending upon whether or not a threshold number of local TCRs are crosslinked by multivalent arrays of the antigen. Variants of Jurkat cells were previously transfected with TCR alpha and beta chains that bind fluorescein, yielding FL-TCR+ human T cells. The transfectants are activated upon binding soluble multivalent antigen arrays at concentrations well below those required for monovalent interactions. This activation, measured by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior binding avidity of multivalent ligands. Smaller, less multivalent arrays do not activate the cells, but antagonize larger arrays, demonstrating that antigen can bind TCR as either agonist or antagonist. The balance between activation and inhibition depends upon antigen array size, ligand valence, and concentration, indicating that a threshold extent of receptor crosslinking, and not individual perturbations of single TCR, is required for activation by antigen. Approximately 100 stimulatory arrays specifically bind per FL-TCR+ cell at concentrations where IL-2 production is half-maximal.
THE GOLD IN GARBAGE.
Authors: DOUGLAS H. STEWART
Journal: JAMA (1895)

The quest of the Middle Ages was for the stone that would turn lead into gold, but the aim of the nineteenth century seems to be the transmutation of waste into wealth. As a natural consequence, the elaborate and expensive utilization works of Europe, and the various processes of dealing with American garbage have been established. Everybody believes in the gold in a dust heap, but as yet it has not materialized. In the light of practical experiment it seems quite as far from realization as the philosopher's stone—also once an object of universal belief. There is not, to my knowledge, a single public municipal system that is run at a profit in the disposal of garbage, no matter what its promises on paper or in the theoretical stage have been. Every system being subsidized—or costing in operating expenses from 7 cents a ton upward to a dollar or more.
A6.2 The NADPH oxidase 2 (NOX2) mediates an anti-inflammatory response to dead cell debris
Authors: J Hahn, D Kienhöfer, L Munoz, R Holmdahl, G Schett, M Hoffmann
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> In the past, the production of reactive oxygen species (ROS) via the oxidative burst has been associated with the promotion of inflammation and tissue damage. However, recent research has implied that ROS are also important for regulation of inflammation and protection from autoimmune diseases. The focus of this project was to determine the involvement of the oxidative burst in the development of experimental lupus and its regulation of inflammatory properties. <h3>Methods</h3> Lupus and arthritis (rupus) was induced by intraperitoneal injection of 0,5 ml pristane oil in WT and Ncf1** mice carrying a mutation in one of the subunits of the phagocyte NADPH oxidase complex that abrogates ROS-production from NOX2. The progression of lupus/arthritis was followed during a six month period by serological markers and severity of organ involvement. Phagocytosis assays ( <i>ex vivo</i>) were established to distinguish a differential uptake of cellular debris and latex beads in WT and Ncf1** mice via FACS analysis and fluorescence microscopy. The formation of neutrophil extracellular traps (NETs) was investigated in blood and peritonea. <h3>Results</h3> After pristane-injection Ncf1** mice develop strongly elevated levels of typical lupus-autoantibodies, e.g. anti-dsDNA, anti-histone and anti-Sm/RNP, and arthritis. A certain amount of spontaneously occurring autoantibodies was also apparent in Ncf1** mice. Ncf1** mice also spontaneously developed signs of glomerulonephritis and exhibited glomerular deposits of complement and immunoglobulins, further exacerbated by injection of pristane. Interestingly, phagocytosis of secondary necrotic cells in Ncf1** mice was enhanced and skewed towards CD11b<sup>+</sup>Ly6c<sup>high</sup> monocytes, whereas there was no difference in the uptake of inert latex beads between Ncf1** and WT mice unless we coated the beads with immunoglobulin G. Furthermore, the ability of Ncf1** mice to create NETs and aggregated NETs was severely dampened. <h3>Conclusion</h3> The Ncf1** mouse suffers from intensified experimental lupus/arthritis, characterised by autoantibodies directed against surface molecules of dead cells and aggravated organ involvement. The mechanics of the exacerbated autoimmune reaction could be associated to the atypical phagocytosis in Ncf1** mice, which demonstrated a skewed uptake of dead cell debris into inflammatory monocytes. The inability to form aggregated NETs could even prolong the inflammatory loop.
NICE will create standards on obesity and use of tobacco and alcohol
Authors: N. Hawkes
Journal: BMJ (2013)

The National Institute for Health and Care Excellence (NICE) is to create new quality standards for public health, the Department of Health for England has announced.

At NICE’s conference in Birmingham, the health minister Earl Howe said that the first three standards would cover tobacco, harmful alcohol use, and obesity—three topics that he admitted had not been difficult to select. He expected that the new quality standards would provide a key tool for Public Health England in tackling the three issues.

A consultation will follow on other public health issues that NICE will cover, amounting eventually to a “growing portfolio” of quality standards. Since its formation in 1999 NICE had earned a worldwide reputation as …
Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency
Authors: Yutaka Nishigaki, Ramon Martí, William C. Copeland, Michio Hirano
Journal: Journal of Clinical Investigation (2003)

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP). This deficiency of TP leads to increased circulating levels of thymidine (deoxythymidine, dThd) and deoxyuridine (dUrd) and has been associated with multiple deletions and depletion of mitochondrial DNA (mtDNA). Here we describe 36 point mutations in mtDNA of tissues and cultured cells from MNGIE patients. Thirty-one mtDNA point mutations (86%) were T-to-C transitions, and of these, 25 were preceded by 5′-AA sequences. In addition, we identified a single base-pair mtDNA deletion and a TT-to-AA mutation. Next-nucleotide effects and dislocation mutagenesis may contribute to the formation of these mutations. These results provide the first demonstration that alterations of nucleoside metabolism can induce multiple sequence-specific point mutations in humans. We hypothesize that, in patients with TP deficiency, increased levels of dThd and dUrd cause mitochondrial nucleotide pool imbalances, which, in turn, lead to mtDNA abnormalities including site-specific point mutations.
Superior Immune Response to Protein-Conjugate versus Free Pneumococcal Polysaccharide Vaccine in Chronic Obstructive Pulmonary Disease
Authors: Mark T. Dransfield, Moon H. Nahm, MeiLan K. Han, Sarah Harnden, Gerard J. Criner, Fernando J. Martinez, Paul D. Scanlon, Prescott G. Woodruff, George R. Washko, John E. Connett, Nicholas R. Anthonisen, William C. Bailey
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults.We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD. We also posited that older age and prior PPSV23 vaccination would be associated with reduced vaccine responsiveness.One hundred twenty patients with COPD were randomized to PPSV23 (63 subjects) or PCV7 (57 subjects). IgG concentrations were determined by ELISA; functional antibody activity was assayed with a standardized opsonophagocytosis assay and reported as an opsonization killing index (OPK). Increases in serotype-specific IgG and OPK at 1 month post vaccination were compared within and between vaccine groups.Both vaccines were well tolerated. Within each study group, postvaccination IgG and OPK were higher than baseline (P < 0.01) for all serotypes. Adjusted for baseline levels, postvaccination IgG was higher in the PCV7 group than the PPSV23 group for all seven serotypes, reaching statistical significance for five (P < 0.05). PCV7 resulted in a higher OPK for six of seven serotypes (statistically greater for four) compared with PPSV23. In multivariate analyses, younger age, vaccine naivety, and receipt of PCV7 were associated with increased OPK responses.PCV7 induces a superior immune response at 1 month post vaccination compared with PPSV23 in COPD. Older age and prior PPSV23 reduce vaccine responsiveness. Clinical trial registered with www.clinicaltrials.gov (NCT00457977).
Abstract P3-08-17: Objectively measured physical activity in breast cancer survivors
Authors: A Soria, I Pagola, MJ Ortega, L Brea, C Fiuza, H Cebolla, I Palomo, M Montil, D Malón, J Guerra, A Lucia, A Ruiz
Journal: Cancer Research (2013)

Abstract Background: Obesity and physical inactivity are poor prognostic indicators for breast cancer (BC). Cardiorespiratory fitness (VO2max) is a good predictor of survival. Despite preserved LVEF, cardiorespiratory function is impaired in women with breast cancer after the completion of adjuvant therapy. International organizations recommend at least 150 minutes per week of moderate-vigorous physical activity (MVPA). Some studies show that a minority of cancer survivors are meeting the PA recommendations. A limitation of physical activity (PA) research has been the use of self-reported measures. Eligibility criteria: 1) Age 18-79, 2) Able to walk a mile, 3) More than one year from diagnosis, 4) More than 3 months since the last therapy, 5) No evidence of disease. Aims: Objective assessment of physical activity in breast cancer survivors. Adherence to international recommendations. Material and methods: PA was evaluated through accelerometry (600 minutes per day, 5 days per week, 2 week-end days were required to consider as valid accelerometry values). Cardiorespiratory fitness was assessed through the “one-mile test”. Results: 92 women (W) with BC history were included. 86 W were evaluable for accelerometry. 85 W were evaluable for VO2max. Age: 54.02 years (33-77), BMI: 27.89 (SD 8.89), waist perimeter: 89.74 cm (SD 17.37), median time from diagnosis 3.94 years, treatment with anthracyclines 55 W (63.9%), radiotherapy 69 W (80.23%). Accelerometry (86W): Average weekly time MVPA 351.14 min/wk (SD: 168.98). 76 (88%) met international recommendations of PA. Women previously treated with anthracyclines (47 W; 340.25 min/wk), radiotherapy (59 w; 343 min/wk) and both (48 W; 331 min/wk) exercised less than women who did not receive these therapies (8 W; 386 min/wk). This association was not statistically significant. Average VO2max was 24.8 ml/kg/min (SD: 7.6).There was a significant effect of anthracyclines for VO2 max. Women not treated with anthracyclines had a VO2max: 26.41 whereas treated W had VO2max 22.08 ml/kg/min. Discussion: A cohort of Spanish women met international recommendations of PA when it was objectively assessed. This cohort exhibited a poor cardiometabolic and cardiorespiratory profile. Previous exposure to anthracyclines predicted a poorer cardiorespiratory fitness. Specific research to investigate the role of exercise to mitigate that dysfunction in breast cancer survivors is warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-17.