tbuckley/cabot-search huggingface dataset:
Rectal Polyps and Cancer
Authors: Norbert J. Roberts
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Your editorial entitled "Rectal Polyps and Cancer" (<i>JAMA</i>181:720 [Aug 25] 1962) presents some interesting thinking on an important problem. We need additional data to evaluate the significance of these polyps, and you are right in advising that those who believe and those who doubt that such growths are potentially malignant share a responsibility for collecting such data. It occurs to me, however, that someone reading your editorial casually might draw some conclusions which you would not intend. You do include the suggestion that sigmoidoscopies should continue to be a part of the physical examination of adults. However, some physicians reading that "There is increasing evidence that they [adenomatous polyps of the colon and rectum] may have no more sinister significance than benign polyps of the nose..." may be tempted to discontinue performing such examinations. They may rationalize this on the basis of the fact that such
Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals
Authors: Laura Maggi, Veronica Santarlasci, Francesco Liotta, Francesca Frosali, Roberta Angeli, Lorenzo Cosmi, Enrico Maggi, Sergio Romagnani, Francesco Annunziato
Journal: Journal of Allergy and Clinical Immunology (2007)
Why do collaborative research?
Authors: Anisur Rahman
Journal: BMJ (2007)

Much of the most valuable medical research is done by large teams of people, often collaborating across several centres. Examples include randomised controlled trials that prove the efficacy of new forms of treatment and genetic studies that use clinical data from many hospitals to establish the linkage of genes to specific diseases.

Such collaborative efforts are undervalued by academic institutions, to the extent that it could be argued that clinical academics who wish to thrive should avoid taking part in such collaborations—unless they are a lead author. Without colleagues who are prepared to collaborate without gaining the kudos of leading, however, none of these studies could be done.

Are the disincentives to collaboration worse than before? One disincentive is the increasing complexity of documentation that researchers need to carry out any form of study involving patients. A researcher who signs up to recruit patients into any multicentre project—even …
Zfx Facilitates Tumorigenesis Caused by Activation of the Hedgehog Pathway
Authors: Colin J. Palmer, Jose M. Galan-Caridad, Stuart P. Weisberg, Liang Lei, Jose M. Esquilin, Gist F. Croft, Brandon Wainwright, Peter Canoll, David M. Owens, Boris Reizis
Journal: Cancer Research (2014)

The Hedgehog (Hh) signaling pathway regulates normal development and cell proliferation in metazoan organisms, but its aberrant activation can promote tumorigenesis. Hh-induced tumors arise from various tissues and they may be indolent or aggressive, as is the case with skin basal cell carcinoma (BCC) or cerebellar medulloblastoma, respectively. Little is known about common cell-intrinsic factors that control the development of such diverse Hh-dependent tumors. Transcription factor Zfx is required for the self-renewal of hematopoietic and embryonic stem cells, as well as for the propagation of acute myeloid and T-lymphoblastic leukemias. We report here that Zfx facilitates the development of experimental BCC and medulloblastoma in mice initiated by deletion of the Hh inhibitory receptor Ptch1. Simultaneous deletion of Zfx along with Ptch1 prevented BCC formation and delayed medulloblastoma development. In contrast, Zfx was dispensable for tumorigenesis in a mouse model of glioblastoma. We used genome-wide expression and chromatin-binding analysis in a human medulloblastoma cell line to characterize direct, evolutionarily conserved targets of Zfx, identifying Dis3L and Ube2j1 as two targets required for the growth of the human medulloblastoma cells. Our results establish Zfx as a common cell-intrinsic regulator of diverse Hh-induced tumors, with implications for the definition of new therapeutic targets in these malignancies.
TRAF5 Deficiency Accelerates Atherogenesis in Mice by Increasing Inflammatory Cell Recruitment and Foam Cell Formation
Authors: Anna Missiou, Philipp Rudolf, Peter Stachon, Dennis Wolf, Nerea Varo, Peter Aichele, Christian Colberg, Natalie Hoppe, Sandra Ernst, Christian Münkel, Carina Walter, Benjamin Sommer, Ingo Hilgendorf, Hiroyasu Nakano, Christoph Bode, Andreas Zirlik
Journal: Circulation Research (2010)

Tumor necrosis factor receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins for the TNF/interleukin-1/Toll-like receptor superfamily. Ligands of this family comprise multiple important cytokines such as TNFα, CD40L, and interleukin-1β that promote chronic inflammatory diseases such as atherosclerosis. We recently reported overexpression of TRAF5 in murine and human atheromata and that TRAF5 promotes inflammatory functions of cultured endothelial cells and macrophages.This study tested the hypothesis that TRAF5 modulates atherogenesis in vivo.Surprisingly, TRAF5(-/-)/LDLR(-/-) mice consuming a high-cholesterol diet for 18 weeks developed significantly larger atherosclerotic lesions than did TRAF5(+/+)/LDLR(-/-) controls. Plaques of TRAF5-deficient animals contained more lipids and macrophages, whereas smooth muscle cells and collagen remained unchanged. Deficiency of TRAF5 in endothelial cells or in leukocytes enhanced adhesion of inflammatory cells to the endothelium in dynamic adhesion assays in vitro and in murine vessels imaged by intravital microscopy in vivo. TRAF5 deficiency also increased expression of adhesion molecules and chemokines and potentiated macrophage lipid uptake and foam cell formation. These findings coincided with increased activation of JNK and appeared to be independent of TRAF2. Finally, patients with stable or acute coronary heart disease had significantly lower amounts of TRAF5 mRNA in blood compared with healthy controls.Unexpectedly, TRAF5 deficiency accelerates atherogenesis in mice, an effect likely mediated by increased inflammatory cell recruitment to the vessel wall and enhanced foam cell formation.
Saccharin — The Bitter Sweet
Authors: Kurt J. Isselbacher, Philip Cole
Journal: New England Journal of Medicine (1977)

A recently completed Canadian study shows that saccharin can act as a bladder carcinogen in rats.1 As a result, the United States Food and Drug Administration proposes to prohibit the use of saccharin as a food additive. This action is required by a 1958 law, which includes the "Delaney clause" stating that "...no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal...." It has been claimed that the value of the Delaney clause lies in the maximum degree of protection that its unqualified language provides. However, as phrased, the . . .
Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis
Authors: P Kapoor, S V Rajkumar, A Dispenzieri, M A Gertz, M Q Lacy, D Dingli, J R Mikhael, V Roy, R A Kyle, P R Greipp, S Kumar, S J Mandrekar
Journal: Leukemia (2011)
Rate of reflow and reperfusion induced arrhythmias: studies with dual coronary perfusion
Authors: C. Ibuki, D. J Hearse, M. Avkiran
Journal: Cardiovascular Research (1992)

Objective: The aim was to determine the relationship between the rate of reflow and vulnerability to reperfusion induced arrhythmias. Methods: Isolated rat hearts, in which left and right coronary arteries were perfused independently, were subjected to transient (10 min) cessation of flow to the left coronary bed. During the subsequent 10 min of reperfusion, flow in the left coronary bed was regulated to create five different reflow profiles (n=12 per group): (1) immediate restoration of 100% flow which was maintained throughout reperfusion (control); (2) stepwise restoration of flow with 10% flow from 0-1 min, 20% flow from 1-2 min, 40% flow from 2-3 min, 60% flow from 3-4 min, 80% flow from 4-5 min, and 100% flow from 5-10 min; (3) 10% flow from 0-5 min and 100% flow from 5-10 min; (4) 20% flow from 0-5 min and 100% flow from 5-10 min; and (5) 40% flow from 0-5 min and 100% flow from 5-10 min. Results: There were no significant differences between the groups in the incidences of reperfusion induced ventricular tachycardia or fibrillation, which were 100% and 58-92%, respectively. However, the time to onset of reperfusion induced ventricular fibrillation was delayed (p<0.05) from 15 (SEM 1) s in group (1) to 191(39), 210(38), and 77(29) s in groups 2, 3, and 4, respectively. No significant delay was observed in group 5. There were no significant differences between the groups in size of ischaemic zone or heart rate. Conclusions: In crystalloid perfused hearts, restricted reflow delays the time to onset of reperfusion induced ventricular fibrillation but does not reduce the incidence of reperfusion induced ventricular tachycardia or fibrillation.
Endometriosis of the lung: A case report and brief review of the literature
Authors: T. Jelihovsky, A. F. Grant
Journal: Thorax (1968)

A case is described of endometriosis of the lung in a symptomless 54-year-old woman. This and the 11 previously recorded cases of histologically examined pulmonary endometriosis have been divided into two groups. Six of these women had died during pregnancy or shortly after delivery, and their lungs contained deposits of decidua but no endometrial glands; the remaining six patients, at least five of whom had had previous pregnancies, had surgically resected lung specimens showing larger single lesions with endometrial glands. The possible relationship between these two groups is discussed.
Reviews: Osteoporosis: Diagnostic and Therapeutic Principles
Authors: Bart L. Clarke
Journal: Annals of Internal Medicine (1997)

Medical Writings15 January 1997Reviews: Osteoporosis: Diagnostic and Therapeutic PrinciplesBart L. ClarkeBart L. ClarkeSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-2-199701150-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Rosen CJ; ed. 297 pages. Totowa, NJ: Humana Pr; 1996. $99.50. ISBN 0896033740. Order phone 201-256-1699.Field of medicine: Endocrinology and metabolism.Format: Hardcover book.Audience: Primary care physicians, endocrinologists, rheumatologists, gynecologists, orthopedic surgeons, and physicians in training.Purpose: To educate a broad array of health care providers about the pathogenesis and treatment of osteoporosis.Content: Describes the pathogenesis and treatment of osteoporosis and details the clinical treatment of osteoporosis. Includes case studies that illustrate specific aspects of osteoporosis care.Highlights: This book provides useful practice guidelines. A unique feature is an appendix that lists the costs of laboratory tests ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1997Volume 126, Issue 2Page: 176KeywordsEndocrinologyHealth care providersLaboratory testsOrthopedicsOsteoporosisPathogenesisPrimary care physiciansSurgeons ePublished: 15 August 2000 Issue Published: 15 January 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Violence on the Screen — Bogus Doctors — Hazards of Practice
Authors: John Lister
Journal: New England Journal of Medicine (1977)

At a time when violence of all kinds is so prevalent throughout the world, it is not surprising that there should be interest in identifying any possible contributory cause. The effect of exposing young people to the portrayal of acts of violence on the television screen has often been debated, and a paper on the topic presented by Dr. William Belson1 at the recent meeting of the British Association for the Advancement of Science aroused considerable interest. He reported the findings of his survey, supported by the Columbia Broadcasting System, on the television-viewing habits and subsequent social behavior of a . . .
Clear winners and losers are created by age only NHS resource allocation
Authors: C. L. Bambra
Journal: BMJ (2012)

<h3>Abstract</h3> In primates, the dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices are critical nodes in the network mediating cognitive functions including attention and working memory. Notably, during working memory tasks, gamma oscillations, usually prominent in layer 3 (L3), are induced in both DLPFC and PPC but exhibit higher frequency in DLPFC. These oscillation frequency differences might be crucial for working memory function, but the mechanisms producing different oscillation frequencies in monkey DLPFC and PPC remain poorly understood. To investigate the basis of the DLPFC-PPC differences in oscillation frequency we studied GABA<sub>A</sub>R-mediated inhibition, which plays a crucial role in gamma oscillation production, in L3 pyramidal neurons (L3 PNs) from the rhesus monkey DLPFC or PPC. Recordings of GABA<sub>A</sub>R-mediated synaptic currents from L3 PNs, while suggesting a contribution to network synchronization in both areas, revealed no DLPFC-PPC differences in the strength or kinetics of GABA<sub>A</sub>R-mediated inhibition. Likewise, the expression of GABA<sub>A</sub>R genes in L3 PNs did not differ between regions. In the absence of differences in inhibition, DLPFC L3 PNs showed greater dendritic spine density and higher expression of AMPAR and NMDAR subunit genes relative to PPC L3 PNs, suggesting that the excitatory synaptic drive onto L3 PNs could be stronger in the DLPFC. Simulations in computational models of the cortical microcircuit showed that, with constant synaptic inhibition, increasing the strength of recurrent excitatory synaptic drive increased the network oscillation frequency. Hence, the DLPFC-PPC differences in gamma oscillation frequency could depend on stronger recurrent excitation in the DLPFC relative to PPC. <h3>Significance statement</h3> Gamma oscillations may contribute to the neural substrate of working memory and exhibit a higher frequency in the prefrontal (DLPFC) than parietal (PPC) areas of primate cortex. To investigate the basis of these oscillation frequency differences which may be crucial for working memory encoding, we studied GABA<sub>A</sub>R-mediated inhibition on L3 pyramidal neurons (L3 PNs) from rhesus monkey DLPFC or PPC. Our data revealed no DLPFC-PPC differences in GABAAR-mediated inhibition but showed greater dendritic spine density in DLPFC L3 PNs, suggesting stronger excitatory synaptic drive. Simulations in computational network models showed that stronger recurrent excitatory synaptic drive increased the network oscillation frequency, suggesting that the higher oscillation frequency could depend on stronger recurrent excitation in the DLPFC relative to PPC.
In vitro basal lamina formation may require non-epidermal cell living substrate*
Authors: DAVID WOODLEY, MARCELLE REGNIER, MICHEL PRUNIERAS
Journal: British Journal of Dermatology (1980)

In an adult human epidermal cell culture system in which three different types of dermo-epidermal junctions could be observed, the in vitro synthesis of basement membrane and type IV collagen was studied with electron microscopy and indirect immunofluorescence via an antiserum to type IV collagen. Essentially, keratinocytes juxtaposed to non-living substrate did not produce either type IV collagen or an ultrastructural basement membrane, whereas both products were found at dermoepidermal junctions composed of living keratinocytes juxtaposed to living dermis. This suggests that the microenvironment of the keratinocyte may influence the synthesis of junctional components.
Myocardial adrenergic denervation supersensitivity depends on a postreceptor mechanism not linked with increased cAMP production.
Authors: H K Hammond, D A Roth, C E Ford, G W Stamnas, M G Ziegler, C Ennis
Journal: Circulation (1992)

BACKGROUND Two major hypotheses have been proposed to explain catecholamine supersensitivity after myocardial denervation, but neither sufficiently explains certain features of the phenomenon. In addition, a nonsurgical method for long-term myocardial adrenergic denervation is desirable but has not been accomplished or described with respect to catecholamine supersensitivity. METHODS AND RESULTS We have accomplished chronic myocardial adrenergic denervation by using 6-hydroxydopamine (6-OHDA). Sixteen weeks after 6-OHDA administration to newborn pigs, we found substantial myocardial adrenergic denervation associated with beta-adrenergic receptor (beta AR) downregulation. Despite decreased beta AR number, the dose of isoproterenol yielding 50% maximal heart rate change (ED50) was decreased, and heart rates during exercise showed increased responsiveness despite decreased circulating catecholamines. Thus, stimulation of fewer receptors yielded an increased response, implying improved signal transduction efficiency. Competitive binding studies with isoproterenol showed an increased proportion of beta AR with high-affinity binding in myocardial membranes from 6-OHDA pigs, suggesting that interaction between beta AR and cardiac G, may contribute to improved signal transduction efficiency. However, measures of adenylyl cyclase activity indicated marked reduction in beta AR-dependent and G2-dependent cAMP production in myocardial membranes from denervated animals despite a normal amount of cardiac Gs and decreased Gi. CONCLUSIONS We have demonstrated that substantial, long-term myocardial adrenergic denervation is possible using 6-OHDA. Denervation supersensitivity in this model does not depend on enhanced cAMP stimulation but rather depends on postreceptor elements in the beta AR-responsive pathway that may be independent of Gs-activated adenylyl cyclase activity. In this model of adrenergic denervation supersensitivity, beta-receptors, through Gs, may be linked to an alternative effector that drives heart rate responsiveness.
Incidence and Management of Severe Hypoglycemia in 434 Adults with Insulin-dependent Diabetes Mellitus
Authors: Ingrid Mühlhauser, Michael Berger, Gabriele Sonnenberg, Jutta Koch, Viktor Jörgens, Guntram Schernthaner, Vera Scholz, Diplom Pädagogin
Journal: Diabetes Care (1985)

The risk of severe hypoglycemia associated with the particular therapeutic approach of two University hospitals was assessed in 96% of all patients with insulin-dependent diabetes mellitus (IDDM) who had been admitted during a period of almost 3 yr to the diabetic wards of two hospitals and who participated in a structured teaching and treatment program. During a mean follow-up period of 18 mo, 10% of the conventionally treated patients (N = 384; age 30 +/- 13 yr; duration of diabetes 12 +/- 9 yr) and 9% of the CSII-treated patients (N = 50, age 28 +/- 7 yr, duration of diabetes 13 +/- 7 yr, total follow-up period 1093 patient-mo) experienced at least one severe hypoglycemic episode per year, and a total of 123 severe hypoglycemic episodes occurred. In a subgroup of 169 conventionally treated patients, mean glycosylated hemoglobin values decreased from 10.5 +/- 1.9% before participation in the program to 9.2 +/- 2.0% (P less than 0.001) 18 +/- 4 mo thereafter. For the CSII-treated patients, glycosylated hemoglobin values were 9.7 +/- 1.9% before initiation of pump therapy and remained at the upper normal range from 3 mo thereafter throughout the study. There was no relationship between glycosylated hemoglobin levels and the occurrence of severe hypoglycemic episodes. Fifty-three severe hypoglycemic episodes were treated with glucagon injections by the patients' relatives (all but one effectively), 30 were managed by assisting physicians, and 44 led to hospitalization. Thus, successful attempts to improve glycosylated hemoglobin values in an unselected group of patients with IDDM were not associated with an unduly high risk of severe hypoglycemia when compared with the scarce data from the literature.
Development of pituitary adenoma in women with hyperprolactinaemia
Authors: A E Pontiroli, L Falsetti
Journal: BMJ (1984)

increase we would need 20 million patients with 20 million controls.'Again this ignores all the additional practical problems of post- marketing surveillance.3The salutary lesson with postmarketing surveillance is that 10 000 patients are too few to detect rare adverse reactions.Professor Rawlins, like many others, chose the number arbitrarily.That postmarketing studies "are likely to be worthwhile only if they enrol 10 times the number of patients in premarketing trials" is no argument."The Grand Old Duke of York, he had 10 000 men" and he found, like we will in postmarketing sur- veillance, that they do not achieve what is expected of them.
Use of Thiazolidinediones and Risk of Heart Failure in People With Type 2 Diabetes
Authors: Thomas E. Delea, John S. Edelsberg, May Hagiwara, Gerry Oster, Lawrence S. Phillips
Journal: Diabetes Care (2003)

OBJECTIVE—To compare the incidence of heart failure in individuals with type 2 diabetes receiving thiazolidinediones (TZDs) versus other oral antihyperglycemic agents. RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study using a health insurance claims database. The study sample included patients with type 2 diabetes who received an oral antihyperglycemic agent between January 1995 and March 2001. Those with any claims for TZDs were designated “exposed,” and each was compared with five randomly selected unexposed patients. Those with diagnoses of heart failure or who received digoxin or a diuretic in the year before their index date were excluded. The primary measure of interest was incidence of heart failure, which was defined as a hospitalization or outpatient visit with a diagnosis of heart failure. RESULTS—TZD patients (n = 5,441) were younger than control subjects (n = 28,103) but more likely to have coronary artery disease or diabetes complications, receive ACE inhibitors, β-blockers, metformin, or insulin, and have undergone HbA1c tests or eye exams; they also had more comorbidities and higher costs (all P &amp;lt; 0.05). However, TZD use was predictive of heart failure even after controlling for these variables (hazard ratio = 1.7, P &amp;lt; 0.001). Adjusted incidence of heart failure at 40 months was 8.2% for TZD patients and 5.3% for control subjects. CONCLUSIONS—The results of this observational study suggest that TZDs may increase the risk of heart failure. Physicians should use TZDs with caution in patients with heart failure, remain vigilant for manifestations of heart failure in those receiving these drugs (especially patients with cardiovasculopathy), and consider alternate therapies for patients who develop symptoms of heart failure, such as shortness of breath.
Management of Thyroid Papillary Carcinoma With Radioiodine in a Patient With End Stage Renal Disease on Hemodialysis
Authors: ANA M. MELLO, ROSS ISAACS, JEFFREY PETERSEN, SHEILA KRONENBERGER, I. ROSS MCDOUGALL
Journal: Clinical Nuclear Medicine (1994)

Metastatic papillary carcinoma was diagnosed in a 42-year-old woman. The cancer had invaded out of the gland and was present in many lymph nodes. After her surgical procedure, she was advised to have radioiodine. However, the patient had total renal failure and was on dialysis. Studies were carried out using a tracer dose of 2 mCi of radioiodine, demonstrating that approximately 60% of the radioactivity in the body was removed with each dialysis. Calculations indicated that a meaningful dose of radiation could be delivered to residual thyroid and metastases with 100 mCi of radiolodine and the total body radiation would be <100 rad delivered over several days. Based on these analyses, she received 100 mCi of 1–131 on two separate occasions and on follow-up scan, clinical evaluation and thyroglobulin measurement is free of disease.