tbuckley/cabot-search huggingface dataset:
OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).
Authors: N Lin, M Danso, A David, J Muscato, C Ellis, M DeSilvio, A Garofalo, Y Nagarwala, E Winer
Journal: Cancer Research (2011)

Abstract Background Lapatinib in combination with trastuzumab enhanced anti-tumor activity in HER2−positive breast cancer (BC) preclinical models. In patients (pts) with trastuzumab-treated, HER2−positive metastatic (M) BC, treatment with the combination was associated with longer progression-free (PFS) and overall survival (OS) compared with lapatinib alone. In pts with stage II/III BC, preoperative treatment with the combination plus paclitaxel resulted in significantly higher pathological complete response rates compared with paclitaxel combined with either agent alone. This evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2−positive BC. This present study is designed to evaluate whether the addition of lapatinib improves PFS among women with HER2−positive MBC receiving trastuzumab as maintenance therapy. Trial Design In this open-label, Phase III study, pts are stratified by line of treatment (first/second) and hormone receptor status (positive/negative) then randomized 1:1 to receive maintenance treatment with either lapatinib (1000mg once daily, continuously) in combination with trastuzumab (6mg/kg once every 3 weeks [Q3W]) or trastuzumab (6mg/kg Q3W) alone. Pts will receive study treatment until disease progression, death, discontinuation due to adverse events or other reasons. Eligibility Criteria Pts with HER2−positive MBC who have completed 12–24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy and have objective response or stable disease. Pts with stable brain metastasis are eligible if entering the study on second-line treatment. Specific Aims The primary objective is to compare PFS of lapatinib in combination with trastuzumab to trastuzumab as continued HER2 suppression therapy. Secondary objectives are to evaluate OS, clinical benefit rate, safety and tolerability. Statistical Methods Efficacy endpoints will be analyzed in the intent to treat population. A total of 193 PFS events from 280 randomized pts will be required to detect a 50% increase in median PFS in pts who receive lapatinib plus trastuzumab compared with trastuzumab (median PFS time is 27 versus 18 weeks, respectively); hazard ratio of 0.67 with an 80% power and a 1-sided type I error of 0.025. Present and Target Accrual Sixteen of the target 280 pts have been randomized. The trial is currently open for accrual in the United States and Canada. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-02.
Reversible Lymphoma in the Setting of Azathioprine Therapy for Crohn's Disease
Authors: Loic Larvol, Jean-Claude Soule, Agnes Le Tourneau
Journal: New England Journal of Medicine (1994)

To the Editor: The use of immunosuppressive agents after organ transplantation is associated with an increased risk of lymphoproliferative disorders related to Epstein-Barr virus (EBV)1. The risk of these disorders with immunosuppressive therapy for other conditions, such as inflammatory bowel disease, is not well established. We describe a patient in whom a reversible EBV-related lymphoproliferative disease developed during treatment with azathioprine for Crohn's disease. A 33-year-old man had a 13-year history of Crohn's disease involving the whole small bowel. Because the disease was steroid-dependent, azathioprine therapy was started (100 mg per day) in April 1988. After steroids were withdrawn, . . .
Desmond Michael Devane
Authors: M. Devane
Journal: BMJ (2003)

Former general practitioner York (b Gillingham, Kent, 1926; q Guy's Hospital, London, 1951; DPH, DTM&H), died from multi-infarct dementia on 20 March 2003.​2003.




Figure 1




Following a career in the army, serving in Malaysia, Aden, and Singapore, and reaching the rank of lieutenant colonel, Desmond Devane became a family doctor in York from 1968 until his retirement in 1988. His main passion was golf, throughout both his working life and in retirement until his final illness robbed him of this enjoyment. He leaves a wife, Isobel; three children; and six grandchildren.
TUBERCULOSIS OF THE MIDDLE EAR AND MASTOID.
Authors: E. A. CROCKETT
Journal: JAMA (1906)

In this paper I shall report a few cases of tuberculosis of the middle ear and mastoid, all drawn from private practice and observed over a considerable period of years. Of course, under the favorable circumstances of private practice we may expect a more favorable prognosis, both from the increased vitality of cases treated under such favorable conditions and from the fact that the hygienic surroundings can be made as perfect as possible. Still the general conclusions of this paper are true as regards a great many hospital patients seen in the last 16 years, as well as the few cases herein reported. I am sure that cultures taken with special reference to the bacillus of tuberculosis as a routine measure in a large series of cases will show a large number of such infections, which clinically show no diagnostic symptoms. They constitute the majority of the severe mastoid cases
Experience with obatoclax mesylate (GX15-070), a small molecule pan–Bcl-2 family antagonist in patients with relapsed or refractory classical Hodgkin lymphoma
Authors: Yasuhiro Oki, Amanda Copeland, Fredrick Hagemeister, Luis E. Fayad, Michelle Fanale, Jorge Romaguera, Anas Younes
Journal: Blood (2012)
Abstract 1250: Inhibition of pancreatic carcinogenesis by t-CUPM, a dual inhibitor of c-Raf and soluble epoxide hydrolase
Authors: Jie Liao, Wanying Zhang, Sung Hee Hwng, Haonan Li, Aaron T. Wecksler, Ke Ma, Bruce D. Hammock, Guang-Yu Yang
Journal: Cancer Research (2014)

Abstract Mutant Kras activated Raf-MAPK/ERK pathway and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. The soluble epoxide hydrolase (sEH), a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we have synthesized a novel compound of trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM) via modifying the central phenyl ring of sorafenib and confirmed its dual inhibition of sEH and c-Raf by recombinant kinase activity assay. Pharmacokinetic analysis revealed that oral dosing of t-CUPM resulted in the higher blood levels than that of sorafenib throughout the complete time course (48 h). The effect of t-CUPM on the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) was determined in the LSL-KrasG12D/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured for the extents of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high grade mPanIN II/III was significantly suppressed by t-CUPM treatment. Inhibition of mutant Kras-transmitted phosphorylations of MEK/ERK was demonstrated in pancreatic tissues and in vitro pancreatic cancer cells by Western blot assay. qPCR analysis revealed that t-CUPM treatment resulted in significantly decreasing the levels of inflammatory cytokines including TNF-α, MCP-1, as well as VCAM-1, and the levels of Shh and GLI1 (Hedgehog pathway). Analysis of eicosanoid profile revealed a significant increase of the EET/DHET ratio that further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-Raf by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis. (supported by NIH R01CA172431) Note: This abstract was not presented at the meeting. Citation Format: Jie Liao, Wanying Zhang, Sung Hee Hwng, Haonan Li, Aaron T. Wecksler, Ke Ma, Bruce D. Hammock, Guang-Yu Yang. Inhibition of pancreatic carcinogenesis by t-CUPM, a dual inhibitor of c-Raf and soluble epoxide hydrolase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1250. doi:10.1158/1538-7445.AM2014-1250
The hunter school of medicine: plans for a new independent medical school.
Authors: R Smith
Journal: BMJ (1982)

If all goes to plan, a new independent medical school, the Hunter School of Medicine, will open within a year within a quarter of a mile of BMA House in London.The time seems ripe.Firstly, the private medical sector has been expanding rapidly over the past few years, and its expansion has been accompanied by ever louder and more justified accusations that it robs the National Health Service of staff trained at the State's expense.Many people in the private sector admit that they need a medical school.Secondly, the existing medical schools, which receive most of their income from the University Grants Committee, are experiencing a lean time.Finally, "privatisation" is the word of the year, and the present Government is enthusiastic about breaking State monopolies and encouraging private sector initiative.Why shouldn't British medical education follow the same path as British Telecom, British Airways, and, maybe, British Rail?
Measles immunisation in children with allergy to egg
Authors: R Aickin, D Hill, A Kemp
Journal: BMJ (1994)

To examine the occurrence of adverse reactions to measles vaccine given as a single dose to children with egg allergy, and to determine if the administration of single dose to children with a positive result in an intradermal skin prick test with the vaccine is associated with adverse reactions.Review of results of immunisation and prospective study of 96 consecutively presenting children given intradermal skin testing with the vaccine.Children's allergy centre.410 children sensitive to egg referred to the allergy unit for advice about measles immunisation.Nature and severity of reactions associated with the administration of measles vaccine.All children had a positive result in a skin prick test with egg white, and five had a positive result in a skin prick test with vaccine. Of 96 consecutive children, 46 had a positive result in an intradermal test with vaccine. After immunisation with a full dose (0.5 ml) of vaccine adverse reactions were associated with a mild reaction in four children, none of whom required treatment. Only one of the 46 children with a positive result in an intradermal vaccine skin test had a reaction associated with vaccine administration. None of the children with a positive result in a skin prick test with measles vaccine reacted to the vaccine. The rate of minor reactions to the vaccine not requiring treatment was 0.98% (95% confidence interval 0.27% to 2.48%) and serious reactions requiring treatment was 0% (0% to 0.9%).Children with IgE mediated allergic reactions to egg protein should be investigated and managed by practitioners with special knowledge in this subject. Measles immunisation should be performed in a setting where any adverse reactions can be dealt with appropriately. Skin tests and measles vaccine and desensitisation are not necessary.
PD-1–PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma
Authors: Ryo Yamamoto, Momoko Nishikori, Toshio Kitawaki, Tomomi Sakai, Masakatsu Hishizawa, Masaharu Tashima, Tadakazu Kondo, Katsuyuki Ohmori, Masayuki Kurata, Takamasa Hayashi, Takashi Uchiyama
Journal: Blood (2008)
173. Process Design and Scale-Up of New Vaccine Concepts for Biodefense
Authors: Sibylle U. Herzer, Peder Bergvall, Raf Lemmens, Matt Coffey, Walter T. Leps, Peter M. Moore
Journal: Molecular Therapy (2005)

New vaccine delivery constituents such as oligonucleotides, plasmids and infectious non-replicating viruses have created the need to find ways to purify these molecules to high purity. Traditional purification methods for plasmids and viruses are time-consuming and are not easy to scale up. To ensure that vaccines will actually be useful as products in biodefense, it will be necessary to design scaleable (GMP) manufacturing processes. Traditional purification processes such as density gradient centrifugation steps for plasmids are unable to deliver the required quantities anticipated for some of the vaccines. Strategies successfully used by manufacturers of therapeutic proteins, need to be adapted for process optimization, because virus and plasmids behave differently from proteins due to their size and shear sensitivity. Purification needs should be addressed as early as possible so that promising vaccine candidates can be produced in sufficient quantities for clinical trials and delivery to market.
Interleukin 3 perfusion in W/Wv mice allows the development of macroscopic hematopoietic spleen colonies and restores cutaneous mast cell number.
Authors: C Ody, V Kindler, P Vassalli
Journal: The Journal of Experimental Medicine (1990)

The genetically anemic W/Wv mice are characterized by the inability of their bone marrow cells to form macroscopic pluripotent hematopoietic colonies in the spleen of irradiated recipients upon transfer (colony-forming units). Furthermore, they almost totally lack mast cells, notably in the skin. In the present study, we have tested the effect of recombinant murine interleukin 3 (rmIL-3) on W/Wv mice hematopoiesis. Transfer of W/Wv bone marrow cells into lethally irradiated recipients perfused with rmIL-3 is followed by the appearance of macroscopic spleen colonies. Moreover, perfusion of rmIL-3 in W/Wv mice: (a) restores almost normal total numbers of hematopoietic precursors (colony-forming cells), but without modification of anemia; and (b) leads to the appearance of a normal number of mastocytes in the skin.
Management of Angioma
Authors: Elmer C. Paulson
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In the article "Management of Angiomas" inThe JournalOct. 15, 1960, Dr. D. J. Kindel relates his experience with soft and ultrasoft irradiation and concludes that this is the ideal treatment of certain infantile angiomas. There is no argument with his observation that the lesions respond to this therapy. Nevertheless, there are sound reasons why many radiologists and dermatologists refuse to use it. In the first place, the 15- and 20-year follow-up is more important than the 6-month or 1-year follow-up in these cases. If the patient acquires an area of skin atrophy or malignancy at the site of treatment 20 years later, neither she nor her family nor her doctor is going to be pleased. The author makes only cursory reference to late sequelae and states they can be avoided by "adequate equipment and training." He does not define this term; neither does he give
Tumor Necrosis Factor and Hypermetabolism
Authors: Timothy B. Seaton
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 May 1990Tumor Necrosis Factor and HypermetabolismTimothy B. Seaton, MD, Nancy Coombe, Abraham Mittelman, MDTimothy B. Seaton, MDSearch for more papers by this author, Nancy CoombeSearch for more papers by this author, Abraham Mittelman, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-9-715_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The role of tumor necrosis factor (cachectin) in the pathogenesis of cachexia from cancer and other chronic diseases remains to be fully explored. Tumor necrosis factor (TNF) inhibits lipoprotein lipase in vitro and causes depletion of fat stores and muscle wasting in animal models (1). We suggest that TNF may also be responsible for alterations in resting metabolic rate.We measured the resting metabolic rate and respiratory quotient in the fasting state by indirect calorimetry in two patients receiving a 24-hour infusion of human recombinant TNF-alpha (200 µg/m2body surface area daily) as part of a phase...References1. Beutler B and Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987;316:379-85. CrossrefMedlineGoogle Scholar2. Starnes H, Warren R, and Jeevanadam M. Tumor necrosis factor and the acute metabolic response to tissue injury. J Clin Invest. 1988;82:1321-5. CrossrefMedlineGoogle Scholar3. Tracey K, Lowry S, and Fahey T. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gyn Obs. 1987;164:415-22. MedlineGoogle Scholar4. Balkwill F, Burke F, and Talbot D. Evidence for tumor necrosis factor/cachectin production in cancer. Lancet. 1987;2:1229-32. CrossrefMedlineGoogle Scholar5. Russell D, Shike M, and Marliss E. Effects of total parenteral nutrition and chemotherapy on the metabolic derangenments in small cell lung cancer. Can Res. 1984:1706-11. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Timothy B. Seaton, MD; Nancy Coombe; Abraham Mittelman, MDAffiliations: New York Medical College at Westchester County Medical Center Valhalla, NY 10595 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNutritional Parameters Observed During 28-Day Infusion of Recombinant Human Tumor Necrosis Factor-αInvited Review: Cytokine Mediators of Malnutrition: Clinical ImplicationsTumor necrosis factor 1 May 1990Volume 112, Issue 9Page: 715-716KeywordsAnimal modelsBody surface areaFatsHypermetabolismLipasesLipoproteinsMusclesPathogenesisTumor necrosis factor ePublished: 1 December 2008 Issue Published: 1 May 1990 PDF downloadLoading ...
Corticosteroids in Infectious Mononucleosis
Authors: T. C. Chalmers, H. Muench
Journal: JAMA (1967)

<h3>To the Editor:—</h3> A paper by Charles E. Bender, MD (<b>199</b>:529, 1967) evaluates the effect of treatment with corticosteroids on the outcome of infectious mononucleosis. This was done by comparing patients preselected for such treatment with those receiving no steroid, on a retrospective basis. An attempt was made to remove extraneous differences by selecting an untreated "control" patient for each steroidtreated patient on the basis of similarity in age, sex, disease status, and time of "treatment." It is most difficult to establish comparable groups in this way. Inevitable uncontrolled differences are not taken into account. Moreover, the author says: The usual approach to an assessment of drug effect by assignment of patients to treatment and control groups was inappropriate because of the well recognized dangers of steroid therapy and because many students treated by the Student Health Service are minors. This seems almost to guarantee the existence of differences
Points: Introduction of 100 unit insulin
Authors: K A Harden
Journal: BMJ (1983)

December, p 1617) of a patient in whom atenolol treatment apparently precipitated renal artery thrombosis.Recent reports suggest that the angiotensin converting enzyme inhibitor captopril may cause the same complication in patients with pre-existing renal artery stenosis.Oelkers' has described two patients with renovascular hypertension who developed renal artery occlusion during treatment with captopril, and, according to Hollenberg,' about 10% of patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney developed rapidly progressive renal failure during the first few weeks of treatment with captopril.Half of these patients recovered renal function with a reduction in dosage of captopril.No details of the remaining patients were given, but one might speculate that some or all of them may also have developed renal artery thrombosis.
Trust in Numbers
Authors: A. Oakley
Journal: BMJ (1995)

Theodore M Porter Princeton University Press, pp 310 ISBN 0 691 03776 0

Few of us probably think of science as a solution to the problem of trust. Yet concepts such as objectivity and validity are the mark of a society that is no longer organised around personal knowledge and local communities. Such a society calls for a type of knowledge capable of seeming to be independent of particular people. This is science.

As we all now know, science is socially constructed: who scientists are and where and when they live help to explain the science they do. Yet, as Theodore M Porter, a historian of science, rightly points out in Trust in Numbers, understanding that science is a social product in no …
1901-121 Profound Inhibition of Arterial Thrombosis by a Novel Nitric Oxide Donor
Authors: Sanjay Kaul, Tasneem Z. Naqvi, Michael C. Fishbein, Bojan Cercek, James S. Forrester, Mia D. Molloy, Juan J. Badimon, Thomas C. Hutsell, Prediman K. Shah
Journal: Journal of the American College of Cardiology (1995)
Scene in Print: Chilean Variation on "How Are You Going to Keep Them Down on the Farm After They've Seen Paree"
Authors: M.-FRANCOISE HALL
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 September 1972Scene in Print: Chilean Variation on "How Are You Going to Keep Them Down on the Farm After They've Seen Paree"M.-FRANCOISE HALLM.-FRANCOISE HALLSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-3-487_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExtramarital intimacy in the three months prior to the interview was reported by 25, 49, 61, and 61 per cent of the married men in the rural, lower, middle, and upper socioeconomic strata, respectively.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: American Journal of Public Health PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1972Volume 77, Issue 3Page: 487-487 ePublished: 1 December 2008 Issue Published: 1 September 1972 PDF downloadLoading ...