tbuckley/cabot-search huggingface dataset:
Lumpectomy plus Tamoxifen with or without Irradiation in Women 70 Years of Age or Older with Early Breast Cancer
Authors: Kevin S. Hughes, Lauren A. Schnaper, Donald Berry, Constance Cirrincione, Beryl McCormick, Brenda Shank, Judith Wheeler, Lorraine A. Champion, Thomas J. Smith, Barbara L. Smith, Charles Shapiro, Hyman B. Muss, Eric Winer, Clifford Hudis, William Wood, David Sugarbaker, I. Craig Henderson, Larry Norton
Journal: New England Journal of Medicine (2004)

In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy.Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival.The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone.Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.
Was George Washington Really the Father of Our Country? A Clinical Geneticist Looks at World History
Authors: Joseph Francis
Journal: JAMA (1994)

Clinical genetics is rarely a topic favored by physicians in training, so teachers of the subject often resort to the "freak show" approach to make it more palatable. Yet, most freaks of nature are anonymous and have little relevance to daily life. How much better, then, to illustrate the subject with historical celebrities, whose lives carry great audience appeal and are now subject to increasingly microscopic (and often molecular) scrutiny. Robert Marion, an academic physician, accomplished lecturer, and popular author (this is his fifth book), here expands upon his student and resident lectures to illustrate for the general reading public the genetic and metabolic disorders affecting prominent world leaders of the last two centuries. The cast could scarcely be more significant: King George III, George Washington, Napoleon Bonaparte, Abraham Lincoln, Tsar Nicholas II, and John F. Kennedy. The book begins with George III, whose "Royal Malady" (porphyria variegata) of recurrent
US jury finds that antidepressant did not cause boy to kill his grandparents
Authors: Jason Cato
Journal: BMJ (2005)

A jury has rejected a claim that the antidepressant sertraline caused a boy to kill his grandparents with a shotgun.

Christopher Pittman was aged 12 in November 2001 when he shot his grandparents in their heads as they slept. He then set fire to the house and fled in a family car. Now 15, he spent three years in a juvenile jail after his criminal trial was delayed when different lawyers and a new judge became involved. Christopher was tried as an adult in Charleston, South Carolina, and was sentenced last week to 30 years' imprisonment. He could have been …
Transient Absence of Hepatic Uptake on Gallium-67 Scintigraphy Following Fludarabine Therapy
Authors: Thien Huynh, Robert Mansberg, Edward Hsiao, Luke Coyle, Paul Roach
Journal: Clinical Nuclear Medicine (2004)

A 61-year-old man with an 8-year history of chronic lymphocytic leukemia became unwell 2 weeks after completion of fludarabine chemotherapy. He developed high fever, coagulopathy, mildly impaired hepatic function, and deteriorating renal function. A gallium study was requested to detect possible disease transformation or the presence of opportunistic lung infection. Corticosteroid therapy was instituted as a result of his deteriorating condition with a prompt clinical response. A dose of 420 MBq gallium-67 was injected within 24 hours of beginning corticosteroids. Scintigraphy at 48 hours after gallium administration (72 hours after beginning corticosteroids) had absent hepatic and splenic uptake of gallium. Delayed imaging on the 5th and 8th days after gallium administration demonstrated recovery of gallium uptake in the liver and spleen as the patient's clinical condition responded to steroid treatment.
Pharmacological inhibition of integrin αvβ3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis
Authors: Eleonora Patsenker, Yury Popov, Felix Stickel, Vreni Schneider, Monika Ledermann, Hans Sägesser, Gerald Niedobitek, Simon L. Goodman, Detlef Schuppan
Journal: Hepatology (2009)

Abstract The vitronectin receptor integrin αvβ3 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation of hepatic stellate cells (HSCs) in vitro. Expecting antifibrotic synergism, we studied the effect of αvβ3 inhibition in two in vivo models of liver fibrogenesis. Liver fibrosis was induced in rats by way of bile duct ligation (BDL) for 6 weeks or thioacetamide (TAA) injections for 12 weeks. A specific αvβ3 (αvβ5) inhibitor (Cilengitide) was given intraperitoneally twice daily at 15 mg/kg during BDL or after TAA administration. Liver collagen was determined as hydroxyproline, and gene expression was quantified by way of quantitative polymerase chain reaction. Liver angiogenesis, macrophage infiltration, and hypoxia were assessed by way of CD31, CD68 and hypoxia-inducible factor-1α immunostaining. Cilengitide decreased overall vessel formation. This was significant in portal areas of BDL and septal areas of TAA fibrotic rats and was associated with a significant increase of liver collagen by 31% (BDL) and 27% (TAA), and up-regulation of profibrogenic genes and matrix metalloproteinase-13. Treatment increased gamma glutamyl transpeptidase in both models, while other serum markers remained unchanged. αvβ3 inhibition resulted in mild liver hypoxia, as evidenced by up-regulation of hypoxia-inducible genes. Liver infiltration by macrophages/Kupffer cells was not affected, although increases in tumor necrosis factor α, interleukin-18, and cyclooxygenase-2 messenger RNA indicated modest macrophage activation. Conclusion: Specific inhibition of integrin αvβ3 (αvβ5) in vivo decreased angiogenesis but worsened biliary (BDL) and septal (TAA) fibrosis, despite its antifibrogenic effect on HSCs in vitro. Angiogenesis inhibitors should be used with caution in patients with hepatic fibrosis. (Hepatology 2009.)
A REMARKABLE CASE OF CARCINOMA OF THE GALL-BLADDER IN A MAN TWENTY-TWO YEARS OLD.
Authors: FREDERICK PROESCHER
Journal: JAMA (1907)

The occurrence of carcinoma in individuals between the ages of 15 and 30 years has been positively established by observations within the last two decades. I shall not speak of congenital carcinoma or that occurring in early childhood. The statistics of Bürger founded on 15,134 autopsies, give 39 cases (25 per cent.) of carcinoma in persons between the ages of 15 and 30 years. None under 15 years are given. De la Camp, in 9,926 cases of carcinoma, found that the patients in 19 or 0.18 per cent. were under 20 years of age. Lubarsch, in 563 cases, found 4 patients between the ages of 14 and 19; 5 between 20 and 25 years and 3 between 26 and 29. Of 527 autopsies on carcinoma cases by Glaser one subject was 20 years of age and 16 were 30 years of age. Of 325 autopsies on carcinoma cases recorded by
Haematological changes in adjuvant disease in the rat. II. Iron metabolism and 51Cr erythrocyte survival.
Authors: M Mikolajew, Z Kuratowska, M Kossakowska, M Plachecka, M Kopec
Journal: Annals of the Rheumatic Diseases (1969)

It has been shown (Mikolajew, Kuratowska, Kossakowska, Plachecka, and Kope,, 1969) that severe anaemia is a frequent finding in postadjuvant disease induced in rats by repeated injections of Freund's adjuvant (FA).The characteristic features of this anaemia were-hypochromicity, macrocy- tosis, high peripheral reticulocytosis, and erythroid hyperplasia of the bone marrow with the arrest of maturation at the stage of basophilic and poly- chromatophilic erythroblast.In the present work, attempts to elucidate the pathogenic mechanisms of postadjuvant anaemia are presented.They include studies on iron meta- bolism and on erythrocyte survival.Incorporation of 59Fe-citrate into Erythrocytes and Organs Carrier-free 1 ,ac.59Fe-citrate (specific activity 5 ptc./hg.Fe) in 1 ml.saline was injected intra-
A History of Surgery: With Emphasis on the Netherlands
Authors: Claude E. Welch
Journal: JAMA (1988)

The author—a surgeon and historian—has succeeded in his two objectives: he has melded the story of Dutch surgery with a comprehensive review of surgery from Hippocrates to the present. The reader can find an enormous amount of information drawn from many sources. Annotations and references abound. Illustrations are interesting and instructive; many have been published here for the first time. Details of social and political history form a necessary background for the theme of the book. In the Netherlands the Golden Age was in the 16th century. The country controlled the seas and was wealthy. Philosophy, science, and the arts flourished; today everyone still recognizes Rembrandt's<i>Anatomy Lesson of Doctor Tulp</i>. Leiden, with its university, and Amsterdam became centers where anatomy and medicine flourished. A succession of wars followed; the preeminence of Dutch medicine was short-lived. Thereafter the Dutch watched the rise of surgery in France, England, and Germany; they
Diabetes-Related Mortality
Authors: Denis Daneman
Journal: Diabetes Care (2001)

Individuals with newly diagnosed type 1 diabetes or members of their families invariably ask questions about the morbidity and mortality associated with this new disorder they must contend with. Some younger children are frightened that the “di” in diabetes means that they will die soon. Teens often use as an excuse for their noncompliance the view that they are going to die young and that nothing they do will alter that course.

What are the facts? And, are they already out-of-date, given recent improvements in diabetes care? Feudtner (1) called type 1 diabetes “ a disease in motion,” citing its “transmutation” from a uniformly lethal condition in the preinsulin era to its present status as a serious chronic disorder based on its long-term morbidity and mortality.

Diabetes-related mortality should be separated in two: deaths occurring early in the course, invariably associated with diabetic ketoacidosis (DKA) or hypoglycemia, and those resulting from long-term micro- and macrovascular complications. The article in this issue of Diabetes Care by Nishimura et al. (2) reports long-term mortality in nearly 1,000 type 1 diabetic patients diagnosed before age 18 years in Allegheny County, Pennsylvania, between 1965 and 1979. They found a significant improvement in survival in the more recently diagnosed individuals and concluded that this improvement likely stems from better glycemic and blood pressure control resulting from the availability of blood glucose monitoring, HbA1c assays, and newer antihypertensive agents.

In life table analyses provided by Nishimura et al. (2) the cumulative survival was 98% at 10 years and 79.6% at 30 years. …
Abstract LB-220: Molecular predictors of sensitivity to an IGF1R inhibitor in pre-clinical models of lung and colon cancers
Authors: Maruja E. Lira, Adam Pavlicek, Nathan V. Lee, Keith O. Ching, Jingjing Ye, Joan Cao, Scott Garza, Kenneth Hook, Mark Ozeck, Stephanie Shi, Jing Yuan, Xianxian Zheng, Paul Rejto, Antonio Gualberto, Julie Kan, James G. Christensen
Journal: Cancer Research (2010)

Abstract Targeting the insulin like growth factor receptor (IGF1R) signaling pathway is a promising approach against a variety of cancers and several clinical trials are now underway designed to evaluate the efficacy of IGF1R inhibitors singly or in combination with chemotherapeutic agents. Identification of the optimal patient population likely to respond is critical to the success of this class of targeted agents. To identify potentially predictive biomarkers, we sought to correlate response to figitumumab (CP-751,871), a fully human monoclonal antibody against IGF1R with molecular characteristics across a panel of cell lines. Growth inhibition to CP-751,871 was assessed in a panel of non-small cell lung carcinoma (NSCLC) (n=27) and colon cancer cell lines (n=21) cultured in anchorage and anchorage-independent conditions. Mutation status, whole-genome mRNA expression and DNA copy number were correlated to drug sensitivity. In addition, RNA expression of key genes in relevant signaling pathways was also interrogated via real time PCR. In the present studies, the frequency of response was greater in colon cancer cell lines than in NSCLC. Tissue or cell origin-specific expression levels of insulin-like growth factor binding proteins (IGFBPs) were associated with sensitivity. Low IGFBP3 expression [p=0.0035] correlated with response in NSCLC cell lines whereas low IGFBP6 [p=0.013] and IGF2BP3 [p=0.038] expression correlated with response in colon cancer lines. Increased IGF1R mRNA [p=0.045] levels, microsatellite stability, and PIK3CA wild-type status were also correlated with sensitivity in colon cancer lines. In addition, high expression of erbB2 [p=0.04] and erbB3 [p=0.04] were also associated with sensitivity of colon cancer lines. Collectively, findings from these studies are of potential value to identify patient populations with increased probability of benefit from IGF1R targeted agents. Our results further indicate that molecular predictors associated with the IGF1R pathway are potentially distinct between lung and colon cancer lines and additional studies to extend to other tumor types are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-220.
Bariatric Surgery — Quick Fix or Long-Term Solution?
Authors: Caren G. Solomon, Robert G. Dluhy
Journal: New England Journal of Medicine (2004)

More than 30 percent of the U.S. population is obese (body-mass index [the weight in kilograms divided by the square of the height in meters], 30 or greater), and 4.9 percent is morbidly obese (body-mass index, 40 or greater).1 The associated risks are substantial. Obese persons have more than 10 times the risk of type 2 diabetes2 and 3 times the risk of coronary heart disease3 of those who are lean, and the risks of these and other coexisting conditions rise with increasing obesity. Mortality increases correspondingly; the risk of death among persons with a body-mass index of 40 or . . .
Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge.
Authors: M Kontakou, R T Przemioslo, R P Sturgess, G A Limb, H J Ellis, P Day, P J Ciclitira
Journal: Gut (1995)

This study investigated the presence of mRNA coding for interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha), and interleukins 2 (IL2) and 6 (IL6), in the mucosa of four coeliac patients in remission who had been challenged with either gliadin or synthetic gliadin oligopeptides. Jejunal biopsy specimens from these patients, taken before and at two, four, and six hours after challenge, were hybridised with specific 35S-labelled DNA oligonucleotide probes. The lamina propria of all the patients contained significantly increased numbers of cytokine mRNA expressing cells four hours after challenge with gliadin or an oligopeptide corresponding to amino acids 31-49 of A-gliadin (peptide A). No significant changes were seen with the peptides corresponding to aminoacids 202-220 (peptide B) or 3-21 (peptide C) of A-gliadin, with the exception of one patient who showed a significant increase in the number of TNF alpha mRNA expressing cells four hours after challenge with peptide B. In vivo studies in coeliac disease have shown that significant histological changes occur in the mucosa of treated coeliac patients four hours after challenge with either gliadin or peptide A. These findings suggest that the histological changes seen previously in the mucosa of coeliac patients after wheat peptide challenge may be caused by increased expression of cytokines within the mucosa.
Protease Inhibitors in the Homeless
Authors: David Bangsberg
Journal: JAMA (1997)

Homeless people are often thought not to adhere to therapy. Should we try to make protease inhibitors available to them? The new therapies for human immunodeficiency virus (HIV) infection are expensive, and their use may lead to the development of drug resistance. Do these drawbacks outweigh the ethical imperative to make effective drugs available to an underserved population? In late 1995, the first protease inhibitor was licensed by the Food and Drug Administration for persons infected with HIV. In combination with reverse transcriptase inhibitors, protease inhibitors give unprecedented improvements in CD4<sup>+</sup>cell count, viral load, morbidity, and mortality.<sup>1</sup>One press report used the term "Lazarus effect"<sup>2</sup>to describe the return to functional status of some patients with end-stage acquired immunodeficiency syndrome (AIDS). Driven by both science and enthusiasm, the standard of care for HIV-infected patients has quickly become combination antiretroviral therapy with a protease inhibitor.<sup>1,3</sup>The price
Retinoids and the gastric mucosa
Authors: P.V. Harrison
Journal: British Journal of Dermatology (1983)

Journal Article Retinoids and the gastric mucosa Get access P.V. Harrison P.V. Harrison Department of Dermatology, Beaumont Hospital, Slyne Road, Lancaster LA1 2JF Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 1, 1 July 1983, Pages 123–124, https://doi.org/10.1111/j.1365-2133.1983.tb04005.x Published: 01 July 1983
Immune Thrombocytopenia After α-Interferon Therapy in Patients With Cancer
Authors: E. A. Abdi
Journal: JAMA (1986)

To the Editor.—  The recent report by McLaughlin et al1deserves some comments. Criteria considered in making a diagnosis of drug-induced immune thrombocytopenia include the following: (1) a consistent clinical history of exposure to drug, (2) exclusion of all other causes, (3) recurrence of thrombocytopenia after rechallenge with the drug, and (4) a positive in vitro test showing a specific drug-dependent effect on platelets.2This report fails to satisfy several of these criteria. First, other causes have not been excluded. We are not given any information about other drugs given concurrently. Almost all patients receiving interferon require an antipyretic agent and many also require antiemetics. The possibility of other drugs causing immune thrombocytopenia has not therefore been excluded.  We are not informed if any of these patients had antecedent viral or bacterial infection that may have caused immune thrombocytopenia. After rechallenge with interferon, thrombocytopenia should occur again, which
Novel mechanism of C-reactive protein for enhancing mouse liver innate immunity
Authors: Akihito Inatsu, Manabu Kinoshita, Hiroyuki Nakashima, Jun Shimizu, Daizoh Saitoh, Seiichi Tamai, Shuhji Seki
Journal: Hepatology (2009)

Although C-reactive protein (CRP) is a representative acute-phase protein produced by hepatocytes, the role of CRP in liver innate immunity remains unclear. Using C57BL/6 mice, the present study investigated how CRP affects the functions of liver macrophages, Kupffer cells, and natural killer / natural killer T (NK/NKT) cells under various conditions, including Escherichia coli infection, septic shock, and multiorgan dysfunction induced by interleukin (IL)-12/lipopolysaccharide (LPS) (generalized Shwartzman reaction [GSR]), and LPS-induced lethal hepatitis in Propionibacterium acnes–primed mice. When mice were challenged with a lethal dose of E. coli, synthetic CRP peptide decreased the mortality without decreasing serum tumor necrosis factor (TNF), presumably by enhancing the phagocytic activity of Kupffer cells. Synthetic CRP greatly decreased the production of TNF and reactive oxygen species from Kupffer cells and thereby rescued mice after lethal LPS challenge. CRP also decreased the mortality from GSR and lethal hepatitis by inhibiting TNF production from Kupffer cells, especially phagocytosing Kupffer cells. However, interferon-gamma production from NK/NKT cells was generally not so affected. CRP reportedly binds to FcγRI and FcγRII, and the injection of anti-FcγRII/III Ab into mice abrogated TNF production from, but increased the phagocytic activity of, Kupffer cells. Furthermore, CRP pretreatment restored the decreased phagocytic activity of Kupffer cells in burn-injured mice and decreased TNF production by Kupffer cells and thereby inhibited mortality after sublethal E. coli infection. If CRP was injected into mice at 1 hour after lethal E. coli challenge, it slightly but significantly increased the survival rate. Conclusion: CRP thus enhances the phagocytosis of Kupffer cells but decreases their TNF production in a complex manner in which the pathway by way of FcγRII may be involved. (HEPATOLOGY 2009.)
Congenital Cataract Mistaken for Myopia and Amblyopia
Authors: W. W. Cooper
Journal: BMJ (1849)

for Dises of the Eye.FROM the circumstance of three instances having fallen under my notice, in which Congenital Cataract had been mistaken for myopia, and two in which it had been regarded as imperfect sensibility of the retina, it would appear, that such errors are more common than is suspected.The publication of the following may, perhaps, assist the diagnosis of some similar cases, and thus prevent reproach from being cast en the surgeon consulted.CASE I. Margaret Hay, a delicate girl, 15 years of age, was brouglht to me on the 15th of March 1847, for supposed amblyopia.Her mother stated, that her attention was first drawn to her daughter's sight, when she was about five years of age, in consequence of the great difficulty experienced in teaching her to read.For some time, it was considered to be stupidity on her part, and she was frequently punished; but at length, it became evident, that her sight was imperfect.An oculist was consulted, who, it would seem, made but a sutperficial exa- mination of the eyes, and pronounced the case to be dulness of the retina, expressing his opinion that she would " grow out of it" in time.No improvement bad, however, taken place up to the period of my seeinlg her.On placing a book with moderate sized type in her hand, she held it ratber obliquely, about four inches from her eyes, and slowly spelt the words.Beyond the distance of four feet, slhe could merely discern the outline of a face, and her ideas of colour were very imper- fect.There was nothing unnatural in the general aspect of the eyes; but, on close examination, there was an absenee of that blackness of the pupil, so characteristic of a perfectly healthy eye.The irides were very active, and the pupils contracted strongly under light.A drop of atropine was placed in each eye; in about ten minutes, full dilatation of the pupils had taken place, and displayed two greyish sebmitransparent lenticular Cataracts, not filling the dilated pupils, but VOL.I.