tbuckley/cabot-search huggingface dataset:
Anisotropic structural complexities in the genesis of reentrant arrhythmias.
Authors: M S Spach
Journal: Circulation (1991)

T he paper by Brugada et a1l in this issue of Circulation adds importantly to mounting evidence that the anisotropic passive electri- cal properties of cardiac muscle play an important role in atrial2-4 and ventricular5-6 reentrant arrhyth- mias.The anisotropic properties involved are deter- mined at a microscopic size scale (<200 jam) by the alignment of cardiac myocytes, their complex shapes, the distribution of their interconnections (gap junc- tions), and the geometry of interstitial (extracellular) space.These electrical properties are different in the atria and ventricles of normal adult hearts.For descriptive purposes, the different types of anisotro- pic properties have been characterized simply as "uniform" and "nonuniform" anisotropy.7 Normal ventricular muscle generally has uniform anisotropic properties due to the presence of frequent side-to- side electrical connections between cells and groups of cells8,9; such bundles produce low amplitude smooth unipolar extracellular waveforms when prop- agation occurs across cells (transverse propaga- tion).7'8In many normal adult atrial bundles, how- ever, the side-to-side connections are sparse, pro- See p 1296 and 1307 ducing nonuniform anisotropic properties.During transverse conduction this results in small multiphasic (fragmented) extracellular waveforms due to asynchronous firing of adjacent cells or groups of cells.8Additionally, the anisotropic properties of the same structure change from uniform to nonuniform during development following birth,3 with aging,8 and in the border zone of healed myocardial infarcts.10-14Functionally, the different anisotropic properties behave differently in response to the same interven- tion.For example, in human and canine atrial and ventricular bundles early premature stimuli and so- dium channel-blocking drugs produce unidirectional longitudinal conduction disturbances in nonuniform anisotropic bundles but not in uniform anisotropic
miR-155 Drives Telomere Fragility in Human Breast Cancer by Targeting TRF1
Authors: Roberto Dinami, Cristiana Ercolani, Eleonora Petti, Silvano Piazza, Yari Ciani, Rosanna Sestito, Andrea Sacconi, Francesca Biagioni, Carlos le Sage, Reuven Agami, Roberta Benetti, Marcella Mottolese, Claudio Schneider, Giovanni Blandino, Stefan Schoeftner
Journal: Cancer Research (2014)

Telomeres consist of DNA tandem repeats that recruit the multiprotein complex shelterin to build a chromatin structure that protects chromosome ends. Although cancer formation is linked to alterations in telomere homeostasis, there is little understanding of how shelterin function is limited in cancer cells. Using a small-scale screening approach, we identified miR-155 as a key regulator in breast cancer cell expression of the shelterin component TERF1 (TRF1). miR-155 targeted a conserved sequence motif in the 3'UTR of TRF1, resulting in its translational repression. miR-155 was upregulated commonly in breast cancer specimens, as associated with reduced TRF1 protein expression, metastasis-free survival, and relapse-free survival in estrogen receptor-positive cases. Modulating miR-155 expression in cells altered TRF1 levels and TRF1 abundance at telomeres. Compromising TRF1 expression by elevating miR-155 increased telomere fragility and altered the structure of metaphase chromosomes. In contrast, reducing miR-155 levels improved telomere function and genomic stability. These results implied that miR-155 upregulation antagonizes telomere integrity in breast cancer cells, increasing genomic instability linked to poor clinical outcome in estrogen receptor-positive disease. Our work argued that miRNA-dependent regulation of shelterin function has a clinically significant impact on telomere function, suggesting the existence of "telo-miRNAs" that have an impact on cancer and aging.
"THE COMMUNITY OF ORIGIN OF DIPHTHERIA, TYPHOID FEVER AND SCARLATINA."
Authors: H. D. Fry
Journal: JAMA (1884)

Editor of the Journal of the American Medical Association: In yourJournalof August 30, was published a paper upon the above subject, which had been read by Dr. E. O. Bardwell at a recent meeting of the Iowa and Illinois Central District Medical Association. Dr. B. gave, as confirmative evidence of such a theory, examples of the prevalence of one or more of these diseases at different seasons in five different places more or less widely separated, and all in bad sanitary condition. They, if taken singly, might be held to support his theory, but studied collectively and<i>chronologically</i>, tend rather to uphold the opinions of the specificity and the propagation of the poisons of these diseases from one to another place. Typhoid fever had prevailed in all of the places in previous years but failed to appear in any of them in 1882, and diphtheria was endemic that
Concern about "rickets" campaign
Authors: T. Rathwell
Journal: BMJ (1980)

Bayes's theorem and the evaluation of tests SIR,-In Dr C C Spicer's recent excellent article on "Bayes's theorem and the evaluation of tests" (30 August, p 592) three basic assumptions of the theory are not discussed.These are: (1) New cases come from a population for which full incidence and prevalence data are available for the disease in question and its associated symptoms.(2) The population is static.(3) A definite diagnosis is made in every case: in Dr Spicer's example the need, or lack of it, for admission is quite clear in every case.Despite these limitations Bayes's theorem is of proved value in computer diagnosis but does not obviously illuminate the way doctors make diagnoses.
Cardiac abnormalities and exercise tolerance in patients receiving renal replacement therapy.
Authors: R E Bullock, H A Amer, I Simpson, M K Ward, R J Hall
Journal: BMJ (1984)

The exercise tolerance of the survivors of a consecutive group of 100 patients in a renal dialysis and transplant programme was compared with the prevalence of cardiac abnormalities detected by exercise testing, echocardiography, and radionuclide angiography. Fifty four patients attended for investigation 27 (SD 7) months after starting renal replacement therapy. Forty three of them (80%) were receiving antihypertensive treatment. Their performance on a bicycle ergometer exercise test was compared with that of 62 normal subjects and the patients divided into five groups of decreasing ability. The exercise tolerance of the patients was very poor, only 17 performing within the normal range. Impairment in exercise capacity was not explained by the type or quality of renal replacement therapy. Fourteen patients developed ischaemic electrocardiographic changes on exercise. Left ventricular ejection fraction was assessed by gated blood pool scanning in 37 patients; all nine of the patients with an abnormally low radionuclide ejection fraction also had abnormal exercise tolerance. Satisfactory M mode echocardiograms were obtained from 45 of the patients, and only two were normal. Left ventricular hypertrophy was detected in 25 (56%) of the echocardiograms, and abnormalities indicating impaired left ventricular function were common and widespread. Grouping all the abnormal cardiac features together for the patients in each exercise group showed a striking linear trend of increasing proportion of cardiac abnormalities with worsening exercise tolerance among the five exercise groups (p less than 0.001). The proportion of patients becoming unemployed within one year of starting renal replacement therapy similarly increased, from nil to 60% from the best exercise group to the most incapacitated. Twenty nine of the original cohort of 100 patients subsequently died, cardiovascular disease accounting for 12 (41%) of these deaths. Diminished exercise tolerance in patients receiving renal replacement therapy is strongly associated with cardiac abnormalities and reduced employment prospects.
Continuous local electrical activity. A mechanism of recurrent ventricular tachycardia.
Authors: M E Josephson, L N Horowitz, A Farshidi
Journal: Circulation (1978)

Although the mechanism of most episodes of recurrent ventricular tachycardia (VT) is believed to be re-entry, definitive proof of this hypothesis has heretofore been unavailable in man. Using programmed stimulation and ventricular endocardial mapping we studied three patients in whom the initiation of VT was dependent upon developing a critical degree of fractionation and delay in local left ventricular electrograms. When electrical activity spanned diastole, VT ensued. Maintenance of VT was associated with continuous electrical activity resembling "local fibrillation" while termination of VT required cessation of this continuous activity. During sinus rhythm the electrogram recorded from the areas which subsequently developed continuous activity showed markedly fractionated and prolonged electrical activity exceeding 100 msec in duration. We feel these observations of the temporal relationship of continuous activity with the development of VT represent the first documentation of the re-entrant nature of this arrhythmia in man.
Prognostic Value of Lymph Node Dissection in Patients with Muscle-Invasive Transitional Cell Carcinoma of the Upper Urinary Tract
Authors: Marco Roscigno, Cesare Cozzarini, Roberto Bertini, Vincenzo Scattoni, Massimo Freschi, Luigi Filippo Da Pozzo, Alberto Briganti, Andrea Gallina, Umberto Capitanio, Renzo Colombo, Guazzoni Giorgio, Francesco Montorsi, Patrizio Rigatti
Journal: European Urology (2008)
Effects of training on quality of peer review: randomised controlled trial
Authors: Sara Schroter, Nick Black, Stephen Evans, James Carpenter, Fiona Godlee, Richard Smith
Journal: BMJ (2004)

Abstract Objective To determine the effects of training on the quality of peer review. Design Single blind randomised controlled trial with two intervention groups receiving different types of training plus a control group. Setting and participants Reviewers at a general medical journal. Interventions Attendance at a training workshop or reception of a self taught training package focusing on what editors want from reviewers and how to critically appraise randomised controlled trials. Main outcome measures Quality of reviews of three manuscripts sent to reviewers at four to six monthly intervals, evaluated using the validated review quality instrument; number of deliberate major errors identified; time taken to review the manuscripts; proportion recommending rejection of the manuscripts. Results Reviewers in the self taught group scored higher in review quality after training than did the control group (score 2.85 v 2.56; difference 0.29, 95% confidence interval 0.14 to 0.44; P = 0.001), but the difference was not of editorial significance and was not maintained in the long term. Both intervention groups identified significantly more major errors after training than did the control group (3.14 and 2.96 v 2.13; P &lt; 0.001), and this remained significant after the reviewers' performance at baseline assessment was taken into account. The evidence for benefit of training was no longer apparent on further testing six months after the interventions. Training had no impact on the time taken to review the papers but was associated with an increased likelihood of recommending rejection (92% and 84% v 76%; P = 0.002). Conclusions Short training packages have only a slight impact on the quality of peer review. The value of longer interventions needs to be assessed.
Rearrangement of the genes for the beta and gamma chains of the T cell receptor is rarely observed in adult B cell lymphoma and chronic lymphocytic leukemia.
Authors: A C Aisenberg, B M Wilkes, J O Jacobson
Journal: Journal of Clinical Investigation (1987)

We determined the configuration of the genes for the beta (T beta) and gamma (T gamma) chains of the T cell receptor in DNA from 100 consecutive cases of B cell lymphoma and B cell chronic lymphocytic leukemia (B-CLL), and compared the findings with those in 18 T cell neoplasms. In 7 of the 100 B cell specimens, a single nongermline band was detected after digestion with the restriction enzyme BamHI, but the rearrangement could be confirmed with a second restriction enzyme in only two. The B cell fragments were small in size and of limited size diversity when compared with the T cell cases, and germline bands of equal intensity were present. A rearrangement of the T gamma gene was never seen in a B cell sample. In contrast, T cell specimens usually rearranged both alleles of T beta (15 of 18), the rearrangement could be confirmed with a second restriction enzyme (17 of 18), both alleles of the first constant region gene segment of T beta always underwent either rearrangement or deletion, and the T gamma gene was also rearranged or deleted (17 of 18). We conclude that ordered rearrangement of the T cell receptor is a rare event in B cell lymphoma and B-CLL. T cell receptor gene studies allow B and T cell lymphomas to be distinguished from each other and from common acute lymphoblastic leukemia antigen-positive non-T, non-B acute lymphoblastic leukemia.
Policies on drugs in the new Europe.
Authors: T D Griffin
Journal: BMJ (1990)

group who need "more frequent smears, at intervals of three years or less."'I have yet to find a gynaecologist or cytologist who recommends that smears are routinely per- formed other than at least three yearly intervals.Thus all women in the target group fall into the category of those who need more frequent smears, and therefore payment will not be made for all smears.Over 15 years only three of the five smears performed will be paid for if targets are reached.In addition, women who have had hysterectomies are withdrawn from the target figures.However, gynaecological and cytological advice indicates that this group, particularly the older age bracket, also runs the risk of developing malignancy and should have regular smears, even in the presence of negative smears before hysterectomy.Thus not only is payment for cervical smears still not being properly made but the clinical basis from which recall policy is derived is suspect, including the starting age of 25.Perhaps those who arrived at this scheme would explain to women why, although they have a three year laboratory based recall, they might be offered only a five yearly smear if we stick to our contractual requirements.Or perhaps simple sense will prevail and all smears appropriately performed will attract payment on the basis that general practitioners are professional, ethical, and well motivated and really would like to be "working for patients."
Common Malignancies With Uncommon Sites of Presentation
Authors: Odelia Goor, Yoav Goor, Fred Konikoff, Leonor Trejo, Ella Naparstak
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.03.188 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 14645438 Common Malignancies With Uncommon Sites of Presentation CASE 3. EPIGASTRIC DISTRESS CAUSED BY A DUODENAL POLYP: A RARE PRESENTATION OF ACUTE LEUKEMIA Odelia GoorxOdelia GoorSearch for articles by this author , Yoav GoorxYoav GoorSearch for articles by this author , Fred KonikoffxFred KonikoffSearch for articles by this author , Leonor TrejoxLeonor TrejoSearch for articles by this author , Ella NaparstakxElla NaparstakSearch for articles by this author Show More Departments of Hematology, Internal Medicine 6, Gastroenterology, and Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel https://doi.org/10.1200/JCO.2003.03.188 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Information on Patients
Authors: G. Ashforth
Journal: BMJ (1968)

Diamine oxidase plasma concentrations after treatment with heparin were measured and compared with the surface to volume ratio of jejunal biopsy samples assessed by a morphometric technique in patients with untreated and treated coeliac disease and in biopsied controls. As expected, enzyme activity was significantly lower in patients with untreated coeliac disease than in patients on a gluten-free diet and in biopsied controls. No difference was found between treated patients and biopsied controls. There was a significant overall correlation between plasma enzyme activity and surface to volume ratio of jejunal mucosa, although two untreated patients without an overt malabsorption syndrome but with a very low surface to volume ratio had normal enzyme activity. This study shows that in coeliac disease plasma diamine oxidase activity after treatment with heparin does not always mirror the extent of the jejunal lesions, particularly in those patients with minimal or unrelated symptoms who would benefit most from a valid screening test to identify their condition.
Questioning the Treatment of Venous Thromboembolism
Authors: David K. Cundiff
Journal: Annals of Internal Medicine (2002)

Letters16 July 2002Questioning the Treatment of Venous ThromboembolismDavid K. CundiffDavid K. CundiffKailua-Kona, HI 96740 (Cundiff)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-2-200207160-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their review of clinical trials that have influenced the treatment of venous thromboembolism (1), Drs. Hirsh and Bates omitted a crucial study by Nielsen and colleagues (2). The Nielsen study compared anticoagulation with heparin plus phenprocoumon and therapy with phenylbutazone in patients with deep venous thrombosis (DVT). The results of the study were negative: One of 48 patients who received anticoagulants and 0 of 42 patients who received phenylbutazone died of pulmonary embolism. The only other previously published randomized, controlled trials of anticoagulants versus placebo in DVT also showed no benefit with anticoagulation (3, 4).Heparin ...References1. Hirsh J, Bates SM. Clinical trials that have influenced the treatment of venous thromboembolism: a historical perspective. Ann Intern Med. 2001;134:409-17. [PMID: 11242501] LinkGoogle Scholar2. Nielsen HK, Husted SE, Krusell LR, Fasting H, Charles P, Hansen HH, et al . Anticoagulant therapy in deep venous thrombosis. A randomized, controlled study. Thromb Res. 1994;73:215-26. [PMID: 8191414] CrossrefMedlineGoogle Scholar3. Kakkar VV, Flanc C, O'Shea M, Flute P, Howe CT, Clark MB. Treatment of deep-vein thrombosis—a random trial. Br J Surg. 1968;55:858. [PMID: 4879792] MedlineGoogle Scholar4. Ott P, Eldrup E, Oxholm P. [Value of anticoagulant therapy in deep venous thrombosis in the lower limb in elderly, mobilized patients. A double-blind placebo controlled study with open therapeutic guidance. Ugeskr Laeger. 1988;150:218-21. [PMID: 3287734] MedlineGoogle Scholar5. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960;1:1309-12. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Kailua-Kona, HI 96740 (Cundiff) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClinical Trials That Have Influenced the Treatment of Venous Thromboembolism: A Historical Perspective Jack Hirsh and Shannon M. Bates Questioning the Treatment of Venous Thromboembolism Jack Hirsh and Shannon Bates Metrics 16 July 2002Volume 137, Issue 2Page: 144-145KeywordsAnticoagulantsDeep vein thrombosisFood and Drug AdministrationHeparinLow molecular weight heparinLungsPulmonary embolismRandomized trialsVenous thromboembolismVitamin K ePublished: 16 July 2002 Issue Published: 16 July 2002 CopyrightCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The addition of endothelial cell growth factor and heparin to human umbilical vein endothelial cell cultures decreases plasminogen activator inhibitor-1 expression.
Authors: B A Konkle, D Ginsburg
Journal: Journal of Clinical Investigation (1988)

Plasminogen activator inhibitor-1 (PAI-1) is a specific and rapid inhibitor of tissue plasminogen activator (tPA) and urokinase. Clinical studies suggest that PAI-1 may play a crucial role in the regulation of fibrinolysis. A number of factors modulate PAI-1 activity in endothelial cell culture, and the isolation of PAI-1 cDNA now allows study of PAI-1 regulation at the mRNA level. We examined the effect of endothelial cell growth factor (ECGF) and heparin on PAI-1 expression in human umbilical vein endothelial cell (HUVEC) culture. The addition of ECGF and heparin to HUVEC cultures results in a 3-10-fold decrease in the PAI-1 activity secreted into the conditioned media. This effect is mediated at the mRNA level. A decrease in PAI-1 is also seen with higher concentrations of ECGF alone, but is greatly enhanced by the addition of heparin. No significant change in tPA antigen or mRNA levels was observed.
Opsonins in the hepatic clearance of pneumococci
Authors: B. A. Runyon
Journal: Hepatology (1987)

An in situ isolated, perfused rat liver system was used to evaluate various opsonins for hepatic trapping and killing of encapsulated, virulent, type 3 pneumococci. Pneumococci were rapidly trapped in the liver in the presence of all potential opsonins including Hanks balanced salt solution with added colloid. However, with some of the potential opsonins the organisms remained viable and could be recovered from the liver. With others there was killing of pneumococci. The combination of rat antibody and complement was effective as an opsonin and produced about the same degree of killing as the same human components. When tested separately killing was not promoted by rat complement, human complement, or human antibody. However, when ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid-Mg2+ was added to block the classical pathway and preserve the alternative pathway there was significant pneumococcal killing which may have been complement mediated or due to an adverse effect of ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid-Mg2+ on the organisms. Fibronectin and C-reactive protein reduced the number of surviving microorganisms, although the change was not significant. Immunoglobulin G (IgG), IgM, IgG, or IgM with complement, and antibody + the classical complement pathway, significantly reduced survival of the organisms. The best killing occurred with antibody plus complement plus fibronectin, which reduced mean survival to 24% during the 1-h perfusion.
Fluorescent histochemical localisation of quinacrine-positive neurones in the guinea-pig and rabbit atrium
Authors: R. CROWE, G. BURNSTOCK
Journal: Cardiovascular Research (1982)

Quinacrine-fluorescent nerve fibres and nerve cell bodies are described in the right and left atria of the guinea-pig and rabbit. The nerve cells (20 to 35 micrometers in diameter) are found predominantly in the right atrium in both species. The nerve fibres are varicose and innervate both the muscle and many blood vessels. The quinacrine fluorescent neural structures are unaffected by chemical sympathectomy with 6-hydroxydopamine. The distribution of quinacrine-positive nerve fibres and cell bodies are compared to the distribution of adrenergic and acetylcholinesterase-positive nerves in the atrium of both species. Quinacrine fluorescence appears to be selective for non-adrenergic, non-cholinergic nerves and the possibility that it is binding to high contents of ATP discussed.