tbuckley/cabot-search huggingface dataset:
Attempt to Isolate a Virus from Biopsy Material in Cases of Rheumatoid Arthritis
Authors: S. K. R. Clarke
Journal: Annals of the Rheumatic Diseases (1958)

Virus Research Laboratory oftheUniversity ofSheffield, LodgeMoorHospital Itwasthought possible thatrheumatoid arthritis mightbecaused byavirus andthatinthecourse oftheillness this virus mightexist latently inthe cells ofthesynovial membraneoroftheperiarticular connective tissue. Biopsies weretherefore takenfromtheknee joints oftwo patients withactive rheumatoid arthritis andraised erythrocyte sedimentation rates. Onepatient wasawomanaged56,whohadsuffered fromrheumatoid arthritis for8years.Thesecond wasa woman aged25,whohadsuffered from rheumatoid arthritis for3years. Thepieces oftissue, whichweremostly fatand fibrous tissue withalittle synovial membrane, were chopped upandmadeintoplasma-clot roller-tube cultures (Robbins, Weller, andEnders, 1952). The mediumusedcontained 5 percent.horseserum, 5percent. beefembryo extract, and90percent. bovine amniotic fluid. After2 days' incubation, fibroblasts started togrowoutroundthepieces and these gradually formed large sheets. Thesheets of fibroblasts fromCase1continued togrowandlook healthy for8weeksandthereafter gradually disintegrated. Thesheets offibroblasts fromCase2 looked healthy for5weeks, whenareasbegan to appear nearsomeoftheexplants inwhichthecells becamegranular andthendegenerated. For3 weeksthese areasbecamebigger andthencells grewinfromthesurrounding cell sheet andthe holesdisappeared. Thecultures eventually disintegrated aswithCase1. Although thedegeneration inCase2 wasconsidered tobenon-specific, mediumtakenfromthe Case2cultures atthetimesthatthedegenerated areaswereappearing, andmediumandcells harvested 11weeksafter theCase2cultures wereset up,werekeptat-70°C.andtheninoculated into someofthecultures ofCase1andintoplasmaclotcultures ofhumanembryo muscle andbone andofmonkeytestis, allwithgoodgrowths of fibroblasts. Mediumandcells takenfromthe monkeytestis cultures 3and6weeksafter inoculationwereinoculated intocultures ofChang's humanliver cells (Chang, 1954), andintoplasmaclot cultures ofhumanembryomuscle, bone, and lung.Allthese cultures appeared healthy for2to 3weeksandthenshowednon-specific degeneration equally inthetest andcontrol cultures. Therewasnoevidence therefore thatthetissues ofthese patients withrheumatoid arthritis contained a virus capable ofcausing degeneration offibroblasts. Summary
Reduced tissue type plasminogen activator activity of the gastroduodenal mucosa in peptic ulcer disease.
Authors: M A Wodzinski, K D Bardhan, J T Reilly, P Cooper, F E Preston
Journal: Gut (1993)

The gastroduodenal mucosa has a rich blood supply. An active fibrinolytic system is presumably required to maintain vascular patency, and impairment may result in reduced blood flow, focal tissue necrosis, and peptic ulcerogenesis. Tissue type and urokinase type plasminogen activator activity (expressed as mIU/mg protein) and plasminogen activator inhibitor type-1 antigen were assayed in homogenates of gastric and duodenal biopsy specimens taken from patients with: normal endoscopy (controls) (n = 14); active duodenal ulcer (n = 21); healed duodenal ulcer (n = 12); and active benign gastric ulcer (n = 15). In controls mean duodenal tissue type plasminogen activator activity was 4110 and urokinase type plasminogen activator activity 150; gastric tissue type plasminogen activator was 2760 and urokinase type plasminogen activator 170; plasminogen activator inhibitor type-1 was generally undetectable. At the edge of active duodenal ulcers tissue type plasminogen activator was considerably reduced, 2220 (p &lt; 0.001) whereas urokinase type plasminogen activator was raised, 290 (p &lt; 0.01). At the edge of active benign gastric ulcers tissue type plasminogen activator was substantially reduced, 1160 (p &lt; 0.001) but urokinase type plasminogen activator was unchanged. At the scar of healed duodenal ulcers tissue type plasminogen activator was slightly reduced, 3290, but urokinase type plasminogen activator was increased, 308 (p &lt; 0.05). H2 receptor antagonist treatment had little effect on tissue type or urokinase type plasminogen activator activity. Plasminogen activator inhibitor type-1 was increased at the edge of active ulcers (p &lt; 0.05) especially when tissue type plasminogen activity was low (r = -0.61, p &lt; 0.05). These findings are consistent with the hypothesis that impaired fibrinolytic activity may be implicated in peptic ulcerogenesis.
The Etiology of Phthisis
Authors: P. Eade
Journal: BMJ (1869)

THE BRITISH MEDICAL 7OURNAL 4&1, the same experiment with asparagus was tried ois Eng, with similar gapults.They hatve nfot pased candrryy through life witliotit a quar<rel."Their mother spoke of one occurring when they wete eiglt years of age;,ud again, while on their first voyage from Siam to America, one of 'them wished to bathe, as was their ckstom, to whicht the other objected, t,s the (lay was col(l.The difference was soon ad(justed; those rare exceptions proving the rule rather than the reverse.
954-7 Cardioversion of Atrial Flutter: Atrial Appendage Stunning and Thromboembolic Potential. A Transesophageal Echocardiographic Study
Authors: Lawrence Baruch, Selvakumar Chockalingam, Vicki Shields, Davendra Mehta, Ene Stern, Calvin Eng
Journal: Journal of the American College of Cardiology (1995)
Immunosuppression in IDDM: Rationale, Risks, Benefits, and Strategies
Authors: Jeffrey L Mahon, John Dupré, Calvin R Stiller, Allan P Donner
Journal: Diabetes Care (1990)

Lipton et al. (this issue, p. 776) in their article "Cyclosporin Therapy for Prevention and Cure of IDDM: Epidemiological Perspective of Benefits and Risks" discuss the definitive assessment of immunotherapy in preclinical and overt IDDM.They focus on the effects of cyclosporin A (CsA) in insulin-requiring patients with recent onset of the disease.The authors contend that an epidemiological approach is necessary in determining the eventual role of immunointervention in IDDM, that such trials must fully assess long-term adverse and beneficial effects, and that further studies with CsA are not justifiable.Their discussion raises important points concerning the need for experience with an experimental drug in preparation for a definitive study of clinical benefit, including the problem of risks that are identifiable but rare.We argue that continuing assessment of the therapeutic value of immunosuppressive agents, including CsA, in relatively short-term studies is warranted. RECOGNITION OF BENEFIT AND ASSESSMENT OF RISKThe difficulties inherent in establishing a therapeutic role for a new intervention in a disease with acute and chronic manifestations are exemplified by immunosuppression with CsA in IDDM.The experiments were
DNR in the Operating Room
Authors: Stuart J. Youngner, Helmut F. Cascorbi, Jerry M. Shuck
Journal: JAMA (1991)

After nearly two decades of experience, the proper circumstances and procedures for implementing do-not-resuscitate (DNR) decisions have become a standard of care throughout our nation. This standard recognizes not only that cardiopulmonary resuscitation sometimes offers no benefit and may actually harm patients, but also that competent patients have a right to refuse it. Moreover, physicians have an obligation to discuss resuscitation status with patients and their families and to document those discussions and the resulting treatment plan in the medical record. In this issue of<i>JAMA</i>, Walker<sup>1</sup>identifies one important area of clinical practice where the application of DNR policy remains problematic— the operating room. At first glance, sending a DNR patient to the operating room may seem paradoxical. Yet, as Walker points out, terminal patients sometimes require palliative surgery. Furthermore, DNR patients need not be terminal; many of them live to leave the hospital
Septicemic melioidosis. Occurrence following acute influenza A six years after exposure in Vietnam
Authors: P. A. Mackowiak
Journal: JAMA (1978)

Septicemic melioidosis in association with acute influenza A was diagnosed in a Vietnam veteran. The case illustrates that activation of melioidosis can occur long after exposure to a known endemic area and may be precipitated by infections with other common pathogens. Hence, physicians must maintain a high index of suspicion of melioidosis when dealing with unexplained sepsis in Vietnam veterans. Prolonged therapy with appropriate antimicrobial agents is needed to eradicate this infection.
A review of the stroke volume response to upright exercise in healthy subjects
Authors: C A Vella, R A Robergs
Journal: British Journal of Sports Medicine (2005)

Traditionally, it has been accepted that, during incremental exercise, stroke volume plateaus at 40% of V o 2 max. However, recent research has documented that stroke volume progressively increases to V o 2 max in both trained and untrained subjects. The stroke volume response to incremental exercise to V o 2 max may be influenced by training status, age, and sex. For endurance trained subjects, the proposed mechanisms for the progressive increase in stroke volume to V o 2 max are enhanced diastolic filling, enhanced contractility, larger blood volume, and decreased cardiac afterload. For untrained subjects, it has been proposed that continued increases in stroke volume may result from a naturally occurring high blood volume. However, additional research is needed to evaluate the importance of blood volume, or other mechanisms, that influence the stroke volume response to exercise in untrained subjects.
Pentazocine vs Morphine
Authors: Leo J. Cass
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Our conclusions are based upon clinical evaluation of these analgesics. We are well aware, as indicated in our communication, that 40 mg of pentazocine is not equal to 20 mg of morphine sulfate. To extrapolate data, without clinical evidence, and conclude that 90 mg of pentazocine is approximately equal to 20 mg of morphine sulfate may be a satisfactory technique from a purely theoretical point, but could not be of immediate clinical use. To establish the equivalent potency of pentazocine and morphine requires dosages of pentazocine which surpass the analgesic effect of morphine, as well as dosages which provide less pain relief than morphine. Interpolation of the data is now possible. We are, however, extremely reluctant to use extrapolation techniques, especially in view of the nonlinearity of the pain scale. It was unfortunate that we did not include in our study a dosage regimen of 10 mg
Potential benefits of minimum unit pricing for alcohol versus a ban on below cost selling in England 2014: modelling study
Authors: A. Brennan, Y. Meng, J. Holmes, D. Hill-McManus, P. S. Meier
Journal: BMJ (2014)

<b>Objective</b> To evaluate the potential impact of two alcohol control policies under consideration in England: banning below cost selling of alcohol and minimum unit pricing. <b>Design</b> Modelling study using the Sheffield Alcohol Policy Model version 2.5. <b>Setting</b> England 2014-15. <b>Population</b> Adults and young people aged 16 or more, including subgroups of moderate, hazardous, and harmful drinkers. <b>Interventions</b> Policy to ban below cost selling, which means that the selling price to consumers could not be lower than tax payable on the product, compared with policies of minimum unit pricing at £0.40 (€0.57; $0.75), 45p, and 50p per unit (7.9 g/10 mL) of pure alcohol. <b>Main outcome measures</b> Changes in mean consumption in terms of units of alcohol, drinkers' expenditure, and reductions in deaths, illnesses, admissions to hospital, and quality adjusted life years. <b>Results</b> The proportion of the market affected is a key driver of impact, with just 0.7% of all units estimated to be sold below the duty plus value added tax threshold implied by a ban on below cost selling, compared with 23.2% of units for a 45p minimum unit price. Below cost selling is estimated to reduce harmful drinkers' mean annual consumption by just 0.08%, around 3 units per year, compared with 3.7% or 137 units per year for a 45p minimum unit price (an approximately 45 times greater effect). The ban on below cost selling has a small effect on population health—saving an estimated 14 deaths and 500 admissions to hospital per annum. In contrast, a 45p minimum unit price is estimated to save 624 deaths and 23 700 hospital admissions. Most of the harm reductions (for example, 89% of estimated deaths saved per annum) are estimated to occur in the 5.3% of people who are harmful drinkers. <b>Conclusions</b> The ban on below cost selling, implemented in the England in May 2014, is estimated to have small effects on consumption and health harm. The previously announced policy of a minimum unit price, if set at expected levels between 40p and 50p per unit, is estimated to have an approximately 40-50 times greater effect.
Accessory atrioventricular pathways that conduct only in the antegrade direction.
Authors: S C Hammill, E L Pritchett, G J Klein, W M Smith, J J Gallagher
Journal: Circulation (1980)

Patients with accessory atrioventricular pathways that conduct only in the antegrade direction represent an unusual variant of the Wolff-Parkinson-White syndrome. This report describes such patients and compares them with patients with accessory pathways that demonstrate bidirectional conduction. Of 143 patients with single accessory pathways, seven demonstrated exclusive antegrade conduction (study group), 111 demonstrated bidirectional conduction (control group), and 25 demonstrated exclusive retrograde conduction. Study group patients were significantly older than patients in the control group (42 +/- 9.8 years and 31.4 +/- 13.9 years, respectively, p &lt; 0.0001). Refractoriness and conduction characteristics of the accessory pathways in the antegrade direction in the study group were not different from those in the control group. Control group patients presented with atrioventricular reentrant tachycardia (58 of 111), atrial fibrillation (23 of 111), both of these arrhythmias (19 of 111), or no documented arrhythmia (11 of 111). Study group patients presented with only atrial fibrillation (six of seven). An accessory pathway with only antegrade conduction is a rare cause of symptoms in the Wolff-Parkinson-White syndrome. These patients are asymptomatic until atrial fibrillation develops as the patient ages. Despite the absence of retrograde conduction over the accessory pathway, its antegrade functional properties are similar to pathways that demonstrate bidirectional conduction.
The Structure and Biochemistry of Cartilage
Authors: H. R. Catchpole
Journal: JAMA (1974)

In this excellent and recommended text, the authors present an account of cartilage at its scientific growing points. They quote fairly from older and recent literature and present their material in readable form and reasonable compass. The sections on chemistry are most effective, but I was surprised to read that collagen and elastin "exhibit notable similarities in chemical composition"—I have always taught that they had none. The venerable expression "cartilage matrix" is apparently approved, but its nonfibrillar portion, the "ground substance," is mentioned only once or twice and then without definition. Perhaps the authors consider the ground substance a chemical mess unworthy to be mentioned in the same breath as the carefully isolated and purified glycosaminoglycans and proteoglycans. However, when the last glycan has been analyzed, the clinician will still have to cope with the ground substance. Morphology is adequately treated as long as the near-disaster area of cartilage ultrastructure
Effect of Serum Potassium Level upon Risk of Digitalis Toxicity.
Authors: Roger W. Jelliffe
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Effect of Serum Potassium Level upon Risk of Digitalis Toxicity.Roger W. Jelliffe, M.D., F.A.C.P.Roger W. Jelliffe, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-821_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBecause hypokalemia predisposes to digitalis toxicity, the relationships between computed total body glycoside concentration (C) (derived from previously described computer programs), serum potassium levels (K), and the cumulative incidence of digitalis toxicity (T) were examined in 79 patients who did not receive computer-assisted therapy. Seventy-two patients had received digoxin; 7 received other preparations. Glycoside concentration was highly correlated with serum digoxin levels (L) : L = 0.185C -0.416 (P < 0.001). Toxicity was defined as nausea, vomiting, or any new arrhythmia that improved or disappeared when digitalis was stopped.Forty-six patients (58%) had no toxicity; their glycoside concentration averaged 15.4... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Roger W. Jelliffe, M.D., F.A.C.P.Affiliations: Los Angeles, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIndividualizing Digoxin TherapyThe Present and Future State of Individualized TherapyPrefaceDigoxin Level and Clinical Manifestations as Determinants in the Diagnosis of Digoxin ToxicityClinical Applications of Pharmacokinetics and Control Theory: Planning, Monitoring, and Adjusting Dosage Regimens of Aminoglycosides, Lidocaine, Digitoxin, and DigoxinComputer-controlled administration of cardiovascular drugsThe serum digoxin test and digoxin toxicity: a Bayesian approach to decision making.PLASMA POTASSIUM LEVELS IN HYPERTENSIVE PATIENTS RECEIVING FIXED‐COMBINATION DIURETIC THERAPYCapturing clinical expertiseA nomogram for digoxin therapy 1 May 1973Volume 78, Issue 5Page: 821-821KeywordsArrhythmiaAttentionGlycosidesNauseaPotassiumSoftware toolsToxicityVomiting ePublished: 1 December 2008 Issue Published: 1 May 1973 PDF downloadLoading ...
Adolescents and Pediatrics
Authors: Manuel Schydlower
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In their recent article on Reye's syndrome, Varma et al (242:1373, 1979) regard three of their cases aged 16, 18, and 19 years as "nonpediatric." I would like to point out to Dr Varma, his colleagues, and readers ofThe Journalthat in 1972 the American Academy of Pediatrics officially stated that the responsibility of this specialty usually terminates by 21 years of age.<sup>1</sup>The American Academy of Pediatrics has given major emphasis to adolescent health in a recent report of their task force on pediatric education<sup>2</sup>and in the work of their Committee on Adolescence and the recently created Section on Adolescent Health.<sup>3</sup>Moreover, in recent years, numerous pediatric departments have fostered the creation of fellowships to train not only pediatricians, but also internists and family practitioners in adolescent medicine,<sup>4</sup>now recognized by the American Medical Association as a new specialty.<sup>5</sup>
Abstract 3242: New chemical tools for disrupting the MDM2/p53 protein-protein interaction: Identification, synthesis and biological evaluation of a novel class of MDM2/p53 inhibitors
Authors: Daniele Pernazza, Xiaolong Li, Harshani R. Lawrence, Wayne C. Guida, Courtney J. DuBoulay, Shawn Watts, Saïd M. Sebti, Jiandong Chen, Nicholas J. Lawrence
Journal: Cancer Research (2011)

Abstract MDM2 and MDMX function as key regulators of p53 by binding to its N terminus, inhibiting its transcriptional activity, and promoting its degradation. In particular, MDM2 is overexpressed in some of human tumors, and with MDMX contributes directly to loss of p53 function during the development of nearly 50% of human cancers. Due to p53 inactivation, MDM2 in many tumors confers tumor survival; therefore it is an important molecular target for anticancer therapy. Several studies showed that reactivation of wild type p53 in tumor cells can be obtained by disrupting the MDM2/p53 interaction with peptidic, peptidomimetic, and small molecule p53-mimetics. Specific successful examples include the Nutlins and spirooxindole analogs (MI-219 and MI-63). Amongst the peptidic and peptidomimetic inhibitors examined to date, none is nearly as effective as Nutlins and MI-219 in tumor killing in vitro. Hence, new inhibitors against MDM2 and/or MDMX are needed: as cell permeable chemical probes of the p53 pathway in cancer biology, and as templates for structure-based rational design of p53 activators for future therapeutic use. As part of our drug discovery program to identify antagonists of the p53/MDM2 and p53/MDMx protein-protein interactions, a high-throughput in-silico screen of a 3.2 millions virtual library of compounds (from Schrödinger, Inc.). A physical restraint was applied during the screen, in order to mimic binding to the hydrophobic cleft of MDM2 normally occupied by three p53 side chains (F19, W23, and L26) that are critical for MDM2/p53 binding. The top highest ranked 160 compounds were then assessed for their ability to block p53 interaction with MDM2 and MDMx in an ELISA assay. This resulted in the identification of E12/DP3-117, a small molecule disruptor of the p53/MDM2 protein-protein interaction with an IC50 value of 47 ± 14 μM. We will report the synthesis and biological evaluation of focused libraries based on the initial hit and on compounds showing improved activity. Structure activity relationship studies around the hits will be disclosed as well as the outcomes of further rounds of chemical design and biological assessment. Binding of E12/DP3-117 to MDM2 is currently being assessed via co-crystallization and other biophysical techniques. We will describe the use of the crystal structure of p53-like mutant peptides in complex with the N-terminal domains of Mdm2, as the basis for rational design of more potent MDM2 small-molecule/peptide hybrid inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3242. doi:10.1158/1538-7445.AM2011-3242
Effects of diltiazem on triggered activity in canine 1 day old infarction
Authors: W. B GOUGH, R. H ZEILER, N. EL-SHERIF
Journal: Cardiovascular Research (1984)

Triggered activity arising from a delayed afterdepolarisation occurs in canine subendocardial Purkinje fibres 1 day following infarction. Standard microelectrode techniques were used to study small preparations (<50 mm2) in vitro. Diltiazem, 1 mg·litre−1, reversibly suppressed triggered activity by reducing maximum diastolic potential, action potential amplitude and the rate of depolarisation of the delayed afterdepolarisation. Complete quiescence or exit block resulted. The effects of diltiazem were antagonised by elevating extracellular Ca ion concentration. These results suggest that automatic ectopic rhythms 1 day following myocardial infarction, that are the result of triggered activity, are dependent on transmembrane Ca ion movement which diltiazem can directly antagonise.
Nebulized 0.5, 2.5 and 5 ml l-epinephrine for post-extubation stridor in children: a prospective, randomized, double-blind clinical trial
Authors: Paulo Sérgio Lucas da Silva, Marcelo Cunio Machado Fonseca, Simone Brasil Oliveira Iglesias, Emílio Lopes Junior, Vânia Euzébio de Aguiar, Werther Brunow de Carvalho
Journal: Intensive Care Medicine (2011)