tbuckley/cabot-search huggingface dataset:
Abstract S3-01: Breast cancer prevention using anastrozole in postmenopausal women at high risk
Authors: J Cuzick, I Sestak, JF Forbes, M Dowsett, J Knox, S Cawthorn, C Saunders, N Roche, RE Mansel, G von Minckwitz, B Bonanni, T Palva, A Howell
Journal: Cancer Research (2013)

Abstract Background: Third generation aromatase inhibitors are the most effective endocrine treatment for hormone receptor positive breast cancer in postmenopausal women. Here, we assess the efficacy of anastrozole in postmenopausal women who do not have breast cancer, but are at high risk of developing the disease. Methods: A multi-centre randomised placebo-controlled trial of 1mg/day oral anastrozole vs. matching placebo for five years was conducted in 3864 postmenopausal women at increased risk of breast cancer. The primary endpoint was the incidence of breast cancer (including ductal carcinoma in-situ (DCIS) and differences were assessed by the proportional hazards model. Detailed information on adverse events was collected. Results: After a median follow up of 5.03 years, 125 breast cancers were recorded. A 53% reduction (95% CI (32-68%), P&amp;lt;0.0001) was seen in the anastrozole arm. Significant reductions were seen for all invasive (50%), oestrogen receptor positive invasive (58%) and in situ tumours (70%). Fractures were non-significantly higher (8.5% vs. 7.7%, P = 0.3) and musculoskeletal events were significantly higher in the anastrozole arm (1226 vs. 1124, RR = 1.10 (1.05-1.16)) but were very common in both arms (63.9% vs. 57.8%). Vasomotor symptoms were also increased with anastrozole (RR = 1.15 (1.08-1.22)). Cancers at other sites were significantly decreased (40 vs. 70, RR = 0.58 (0.39-0.85)). Deaths from breast cancer and other causes were similar in both arms. Conclusions: Anastrozole is an effective agent for reducing breast cancer incidence in postmenopausal women at high risk. Anastrozole was well tolerated and side effects associated with oestrogen deprivation were only slightly higher than for placebo. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S3-01.
Perianal bowenoid papulosis presenting with pruritus ani
Authors: H.P. Stevens, L.S. Ostlere, M.H.A. Rustin
Journal: British Journal of Dermatology (1993)

British Journal of DermatologyVolume 129, Issue 5 p. 648-649 Perianal bowenoid papulosis presenting with pruritus ani H.P. Stevens, H.P. Stevens Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this authorL.S. Ostlere, L.S. Ostlere Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this authorM.H.A. Rustin, M.H.A. Rustin Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this author H.P. Stevens, H.P. Stevens Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this authorL.S. Ostlere, L.S. Ostlere Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this authorM.H.A. Rustin, M.H.A. Rustin Department of Dermatology, The Royal Free Hospital and School of Medicine, Pond Street, London NW 3 2QG. U.K.Search for more papers by this author First published: November 1993 https://doi.org/10.1111/j.1365-2133.1993.tb00510.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume129, Issue5November 1993Pages 648-649 RelatedInformation
Insulin Allergy Treated with Human Insulin (recombinant DNA)
Authors: I De Leeuw, C Delvigne, J Bekaert
Journal: Diabetes Care (1982)

Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6–9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved.
Meningoencephalitis from<i>Borrelia miyamotoi</i>in an Immunocompromised Patient
Authors: Joseph L. Gugliotta, Heidi K. Goethert, Victor P. Berardi, Sam R. Telford
Journal: New England Journal of Medicine (2013)

Ixodes ticks serve as vectors for Borrelia burgdorferi, the agent of Lyme disease.Globally, these ticks often concurrently harbor B. miyamotoi, a spirochete that is classified within the relapsing-fever group of spirochetes.Although humans presumably are exposed to B. miyamotoi, there are limited data suggesting disease attributable to it.We report a case of progressive mental deterioration in an older, immunocompromised patient, and even though Koch's postulates were not met, we posit B. miyamotoi as the cause, owing to its direct detection in cerebrospinal fluid (CSF) with the use of microscopy and a polymerase-chain-reaction (PCR) assay.It is likely that B. miyamotoi is an underrecognized cause of disease, especially in sites where Lyme disease is endemic. C A SE R EP OR TAn 80-year-old woman was evaluated because of 4 months of progressive decline in mental status, including increasing confusion, withdrawal from family interactions, episodes of not getting out of bed, wobbling gait, and difficulty hearing, accompanied by a decrease in appetite and a 13.6-kg (30-lb) weight loss.Her medical history was notable for non-Hodgkin's lymphoma (follicular type, stage IIA), diagnosed in February 2005.She was treated with a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab from June 2005 through September 2005, and then with rituximab every 6 months until August 2011.The patient also had a history of hypertension and a recent diagnosis of depression.She had no history of travel, no known tick bites or rash, and no recent erythema migrans.She lived on a farm in New Jersey, where there was possible exposure to poultry, cats, dogs, and field mice and where deer were frequently observed.She had been treated twice in the past for Lyme disease: once in November 2006 (clinical details were not available other than a negative result on serologic testing for Lyme disease) and once in July 2007, when she presented with erythema migrans and was treated with doxycycline for 2 weeks.The patient was evaluated by her primary care provider.A metabolic workup was unrevealing, and she was referred to the oncology department.Computed tomography of the chest, abdomen, and pelvis showed no evidence of new disease.Magnetic resonance imaging of the brain, performed with and without the administration of contrast material on February 6, 2012, showed no acute findings.A lumbar puncture was performed on February 21, 2012, to assess the patient for lymphomatous meningitis.Cytologic analysis and flow cytometry showed pleocytosis with an increased protein level (Table 1).Giemsa staining of a cytospin
The Pediatrician and Adoption
Authors: Morris A. Wessel
Journal: New England Journal of Medicine (1960)

SHORTLY after opening an office for the practice of medicine, a physician is faced with many problems quite foreign to his experiences in medical school and hospital training. A common problem in the field of pediatrics is to be asked to evaluate a newborn infant who is being considered for adoptive placement. The request usually comes a few hours after the baby is born. It may come from a social agency offering services to unmarried mothers and adopting couples. Or it may come from a couple who have made arrangements for adopting an infant after having made contact with the . . .
Dextran and intermittent pneumatic compression in prevention of postoperative deep vein thrombosis: multiunit trial.
Authors: R C Smith, R A Elton, J D Orr, A J Hart, I F Graham, G A Fuller, J S Rundle, A I Macpherson, C V Ruckley
Journal: BMJ (1978)

Seven general surgical units co-operated in a clinical trial of dextran 70 and pneumatic calf compression alone and in combination in the preventing of 125I-fibrinogen-detectable deep vein thrombosis in 305 patients. Both dextran regimens were significantly more effective than pneumatic compression alone. Pulmonary embolism was diagnosed in 14 patients, but there was no significant difference in incidence among the three treatment groups. In patients receiving dextran there was no greater median operative blood loss but there was a significantly greater incidence of postoperative bleeding complications.
Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity.
Authors: B K Sharma, R P Walt, R E Pounder, M D Gomes, E C Wood, L H Logan
Journal: Gut (1984)

In a series of 59 experiments in nine duodenal ulcer patients, 24 hour intragastric acidity was measured before, during, and after treatment with daily oral omeprazole. Omeprazole 10, 20, and 30 mg/day for one week caused a 37, 90, and 97% decrease of 24 hour intragastric acidity, respectively. No further decrease of acidity was observed when the dose of omeprazole was doubled to 60 mg/day, or after a second week of treatment with 30 mg/day. One week after stopping treatment with omeprazole (14 doses) there was a significant 26% decrease of 24 hour intragastric acidity, with full recovery seven weeks later. Fasting plasma gastrin concentration was significantly raised during treatment with all doses of omeprazole. Omeprazole 30 mg/day is the optimal dose for a maximal decrease of 24 hour intragastric acidity in duodenal ulcer patients.
Entanglement of a Cardiac Catheter on a Heart-Valve Prosthesis
Authors: E. Berry Hey, Ihor Dyrda, Claude R. Joyner
Journal: New England Journal of Medicine (1966)

THIS report describes an unusual and potentially lethal complication of catheterization of the aortic root that occurred during study of a patient who had previously undergone replacement of the aortic valve with a ball-valve prosthesis (Magovern valve).1 Case ReportM.B., a 23-year-old woman, was admitted to the Hospital of the University of Pennsylvania on October 12, 1965, complaining of chest pain, fatigue, and exertional dyspnea. In July, 1964, a No. 5 Magovern prosthesis had been implanted for the correction of massive aortic insufficiency. After operation she did very well until 1 month before the present admission, when evidence of recurrence . . .
STUDIES ON INFLAMMATION
Authors: Valy Menkin
Journal: The Journal of Experimental Medicine (1932)

A concentrated urea solution effectively dissolves fibrin. The injection into the peritoneal cavity of a urea solution (30 or 50 per cent) together with or after an inflammatory irritant (aleuronat) prevents wholly or in part the local fixation of graphite particles or ferric chloride introduced subsequently. The histologic picture in the retrosternal lymphatics explains how this comes about. When free dissemination of graphite to the retrosternal nodes occurs, the lumen of the lymphatic vessel is unobstructed, whereas partial dissemination is accompanied by small fibrinous thrombi occluding the lumen in part only. Trypan blue injected at the periphery of an inflamed skin area treated with a concentrated urea solution and bacteria (Staph. aureus) penetrates readily into the area, whereas it fails to do so when introduced around an inflamed area consequent on the injection of distilled water and bacteria (Staph. aureus). Concentrated urea per se is an inflammatory irritant. Graphite particles injected into a peritoneal cavity previously treated with concentrated urea penetrate freely to the retrostemal lymphatic nodes; the lymphatic vessel is relatively unobstructed. Trypan blue injected into the circulating blood accumulates rapidly in cutaneous areas almost immediately after the latter have been treated with concentrations of urea ranging from 50 per cent down to 20 per cent. The results of this study furnish evidence, in addition to that already provided, that fixation of foreign substances is primarily due to mechanical obstruction caused by a fibrin network and by thrombosed lymphatics at the site of inflammation. The significance of fixation in relation to immunity and its bearing upon some of the other processes involved in the inflammatory reaction have been stressed.
Possible Anaphylactic Reaction to Intravenous Cyclophosphamide
Authors: Richard K. Karchmer
Journal: JAMA (1977)

THE COMMON side effects and toxicity of cyclophosphamide include nausea, vomiting, immunosuppression, myelosuppression, sterility, and hemorrhagic cystitis.<sup>1</sup>Rarer toxic reactions include the inappropriate secretion of antidiuretic hormone.<sup>1</sup>We have recently observed a patient who had a hypotensive episode and respiratory arrest immediately following an intravenous injection of cyclophosphamide. <h3>Report of a Case</h3> A 66-year-old woman experienced headaches, cervical adenopathy, and bilateral papilledema in September 1971. At surgery, she was found to have a poorly differentiated lymphocytic lymphoma invading the membranous tissue, dura, and bone of the skull. Postoperatively, she received radiation therapy to the skull and the cervical and supraclavicular lymph nodes. The patient was then referred to the University of Utah Medical Center in May 1972. Although her physical examination and bone marrow biopsy specimen showed no evidence of lymphoma, a bipedal lymphangiogram was positive. In June 1972, intermittent chemotherapy was begun. Each course consisted of cyclophosphamide,
Rapid development of exhaustion and down-regulation of eomesodermin limit the antitumor activity of adoptively transferred murine natural killer cells
Authors: Saar Gill, Adrianne E. Vasey, Alysha De Souza, Jeanette Baker, Aaron T. Smith, Holbrook E. Kohrt, Mareike Florek, Kenneth D. Gibbs, Keri Tate, David S. Ritchie, Robert S. Negrin
Journal: Blood (2012)
THE HEREDITARY FACTOR IN ASTHMA AND OTHER ALLERGIES
Authors: G. W. Bray
Journal: BMJ (1930)

DICLJOURNALteinderniiess over the right lower ribs in front anid over the right lhypochonidriuni.There was no dullness, anid nio advenititious sounds could be lheard at the right lunig base.There was no abdominal hyperaestliesia.The diagnosis of diaplhra-grniatic pleuriisy was rnade and conifiiml]ed later by the developmiienit of dullniess at the Lase of the riglht lung.CASE III.W. M., aged 20, on MarCh1 8th, 1921, sUdden1ly felt a stabbing pain under the left collar-hone.The pain onily lasted for half an hour, but came on again that night, and seemed to be worse oni taking a deep breath.It gradually got worse, and by Mar-ch l9th was fairly continu6us.There was giddiness, vomiting, and also epigastr ic pain.When admitted to St. Mary's Hospital on March 19tlh the pain lhad become more precordial, and there was cyanosis.On March 21st a faint pericardial rub was lhear d just out;side the sternum in the third left inter costal space.A few days after admission the patielnt still had a little left subelavicular pa ln.CASE IV.
Abstract 2832: Development of AGS-22M6E, a novel antibody drug conjugate (ADC) targeting Nectin-4 for the treatment of solid tumors
Authors: Daulet Satpayev, Michael Torgov, Peng Yang, Karen Morrison, Yuriy Shostak, Art Raitano, Wendy Liu, Dawn Lortie, Zili An, Linnette Capo, Monica Leavitt, Myra Perez, Alla Verlinsky, Kenna Shirasuna, Hector Avina, Claudia Guevara, Kendall Morrison, Pia Challita-Eid, Xiao-Chi Jia, Jean Gudas, David Stover
Journal: Cancer Research (2011)

Abstract Nectin-4 is a type I transmembrane antigen identified by Agensys to be highly expressed at the RNA level in a significant number of bladder and breast cancer specimens. Analysis of protein expression carried out in an extensive panel of tumor specimens by immunohistochemistry confirmed strong to moderate expression levels of Nectin-4 in bladder, breast and pancreatic cancers (40-60%). A subset of lung and ovarian cancers (up to 30%) also showed significant expression levels of this protein. We have generated an antibody-drug conjugate (ADC) targeting Nectin-4, AGS-22M6E. The highly potent microtubule disrupting drug monomethyl auristatin E (MMAE) was conjugated via valine-citrulline cleavable linker to a fully human IgG1k antibody specific for Nectin-4. AGS-22M6E was characterized for binding affinity, species crossreactivity and cytotoxicity in vitro. AGS-22M6E binds to cell surface Nectin-4 with high affinity and crossreacts with Nectin-4 orthologs of cynomolgus monkey, rat and murine origin. Upon binding to its target on the cell surface AGS-22M6E is internalized and induces cell death in vitro in a dose dependent manner. In vivo efficacy of AGS-22M6E was tested in SCID mice on xenograft models of breast, bladder, pancreatic and lung cancers in subcutaneous and orthotopic modalities. Treatment of well established tumor xenografts with the ADC resulted in significant growth inhibition or complete eradication of tumors in various models covering multiple cancer indications. Pharmacokinetics of AGS-22M6E in non-tumor bearing mice was also evaluated and will be discussed. Overall, these data validate AGS-22M6E as an attractive therapeutic drug candidate for multiple solid tumor indications and support further clinical investigation. 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 2832. doi:10.1158/1538-7445.AM2011-2832
Twenty-eight loci that influence serum urate levels: analysis of association with gout
Authors: A J Phipps-Green, M E Merriman, R Topless, S Altaf, G W Montgomery, C Franklin, G T Jones, A M van Rij, D White, L K Stamp, N Dalbeth, T R Merriman
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets. <h3>Methods</h3> 648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (&gt;0.7) to detect effects of OR&gt;1.3. <h3>Results</h3> We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (<i>IGF1R</i>). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci—two had not previously been associated with gout (<i>PDZK1</i> and <i>MAF</i>). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at <i>PRKAG2</i> and <i>HLF</i> (<i>HLF</i> is the first report of association with gout). There was obvious inconsistency of gout association at four loci (<i>GCKR</i>, <i>INHBC</i>, <i>SLC22A11</i>, <i>SLC16A9</i>) that display very similar effects on urate levels. <h3>Conclusions</h3> We provide the first evidence for association with gout at four loci (<i>IGF1R</i>, <i>PDZK1</i>, <i>MAF</i>, <i>HLF</i>). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.
National academies call for investment in scientific research to be almost doubled to 3% of GDP
Authors: I. Torjesen
Journal: BMJ (2015)

To secure the United Kingdom’s future prosperity the government must ramp up investment in research and development and create a policy environment that supports innovation, the national academies have warned in a joint statement.1

They say investment in research and development needs to be almost doubled from 1.73% of to 3% of gross domestic product. As well as investing in scientific research itself, the next government needs to create an environment that attracts more industrial and charitable investment, emphasises the need for more teachers with specialist subject knowledge at all stages of education, and has the right policies in place to encourage skilled immigration and minimise unnecessary barriers to talented researchers and students.

“Clear messages and policies are crucially needed to counter perceptions that recent changes to immigration policy mean that the UK is closed for business,” the national academies’ statement says.

Cuts to research and innovation …
Recurrent cutaneous Langerhans cell histiocytosis in infancy
Authors: C. W. LEE, M. H. PARK, H. LEE
Journal: British Journal of Dermatology (1988)

We report two infants, aged 4 and 9 months, respectively, who had recurrent cutaneous lesions of Langerhans cell histiocytosis confirmed by immunohistochemical and ultrastructural studies. The lesions were confined to the skin and appeared as transient papules on the trunk in both patients. Since neither showed evidence of internal organ involvement or further recurrences of the skin lesions during follow-up periods of 22 and 24 months, respectively, no therapy was given. These cases may be considered as an uncommon benign variant of the Langerhans cell proliferative disorder.