tbuckley/cabot-search huggingface dataset:
Long acting opioids are linked to increased risk of death
Authors: Jacqui Wise
Journal: BMJ (2016)

Prescription of long acting opioids for chronic non-cancer pain was associated with a significantly higher risk of all cause mortality than anticonvulsants or cyclic antidepressants, US research in JAMA has found.1

Long acting opioids have long been known to increase the risk of unintentional overdose, but this study found that more than two thirds of the excess deaths were due to other causes and that more than half were cardiovascular deaths.

The researchers compared the risk of death in patients starting long acting opioid treatment for moderate to severe chronic non-cancer pain with matched patients starting either an analgesic anticonvulsant or a low …
Evaluating The Utility Of Telomere Length Measurement By Qpcr As a Diagnostic Test For Dyskeratosis Congenita
Authors: Shahinaz M Gadalla, Hormuzd Katki, Neelam Giri, Jason Wong, Stephen Spellman, Mbs, Jack Yanovski, Joan Han, Immaculata De Vivo, Blanche P Alter, Sharon A Savage
Journal: Blood (2013)
Histopathogenesis of Squamouscell Carcinoma Induced in the Forestomach of Mice by Intramural Injection of 20-Methylcholanthrene
Authors: Harlan I. Firminger, Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article Histopathogenesis of Squamouscell Carcinoma Induced in the Forestomach of Mice by Intramural Injection of 20-Methylcholanthrene Get access Harlan I. Firminger, Harlan I. Firminger Pathology Section, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart Harold L. Stewart Pathology Section, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 3, December 1951, Pages 491–531, https://doi.org/10.1093/jnci/12.3.491 Published: 01 December 1951 Article history Received: 23 July 1951 Published: 01 December 1951
Triadic Labeling with I&lt;sup&gt;130&lt;/sup&gt;, I&lt;sup&gt;131&lt;/sup&gt;, and I&lt;sup&gt;133&lt;/sup&gt; for Controlled Determinations of Tumor-Localizing Antibodies&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Eugene D. Day, Jakob A. Planinsek, David Pressman
Journal: JNCI Journal of the National Cancer Institute (1961)

The triadic label technique was developed to provide a method for the comparison of pairs of tumor-localizing antibodies, over and above a variable background localization of nonspecific globulin. The technique involved the labeling of one antiserum globulin with one radioiodine isotope, the other with a second radioiodine isotope, and the control globulin with a third radioiodine isotope. To exemplify the use of the technique, I130, I131, and I133 were selected as triadic labels in two experiments. In one experiment the localizing properties of antihepatoma and antiliver antibodies were compared, over and above the background localization of normal globulin, in rats bearing hepatomas induced by N-2-fluorenylacetamide. In the second experiment the localizing properties of antihepatoma and antirat-plasma antibodies were compared, over and above the background localization of antirat-serum antiserum globulin, in rats bearing induced hepatomas and in normal rats.
The Biological Effects of Some Podophyllin Compounds and Their Dependence on Chemical Structure. II
Authors: M. Maturová, J. Malinský, F. Šantavý
Journal: JNCI Journal of the National Cancer Institute (1959)

Since deoxypodophyllotoxin and cpipodophyllotoxin are of different origin from those compounds used in our previous work, we confirmed their biological inactivity at 200 mg. per kg. The same inactivity was demonstrated for deoxypicropodophyllin. Introduction of a double bond into the B ring of deoxypicropodophyllin and subsequent formation of α-, β-, and γ-apopicropodophyllin restore the toxicity and biological effect on the dividing cell. The effect is fivefold less than that of podophyllotoxin. The toxicity-stathmokinesis index of these compounds is lower than 2, so that the compounds are unsuitable for therapeutic use. Complete aromatization of the B ring of dehydroahydropicropodophyllin is again followed by the loss of the biological activity.
MB-59IMAGING OF METASTATIC MEDULLOBLASTOMA IN THE MOLECULAR ERA
Authors: Michal Zapotocky, Alvaro Lassaletta, Eric Bouffet, Ute Bartels, Annie Huang, Suzanne Laughlin, Uri Tabori, Michael Taylor, Cynthia Hawkins, Charles Raybaud, Vijay Ramaswamy
Journal: Neuro-Oncology (2016)
Soundings: No regrets
Authors: Liam Farrell
Journal: BMJ (2000)

South Armagh is gaily festooned with army bases. For security reasons these bases are supplied exclusively by helicopter, and the helicopters have to travel in threes to protect each other against ground to air attack. This all makes our skies very congested and noisy, but it's an ill wind; we can often call in these helicopters for the urgent transfer of critical patients to hospital, usually either as a result of a road traffic accident or somebody getting kicked in the head by a cow. I've travelled in them a few times, and it was exciting at first; the noise, the speed, the fun of leaning over the pilot's shoulder and pretending to vomit or yelling, “I love the smell of napalm in the morning.”

But the novelty soon palls; it is a bumpy, cramped ride, and when you arrive and hand over the patient's care the hospital staff will patronise you, however tactfully.

One minute you are solely responsible for a patient's life, looking death right in the face, desperate eyes clinging to yours, and the next you are just another Joe wandering the hospital corridors waiting for a ride home. Such an abrupt change of role is curiously unsettling.

We used to have the added excitement of expecting to be blown out of the air at any moment but now even that little thrill is gone, though it is a thrill I am happy to forgo. To paraphrase Trollope, the troubles have delighted me for long enough.

I'm not sure a political solution is really all that vital. As the level of education improves and the standard of living rises and more people travel the world and achieve a sense of perspective, the stupidity of creeds based on slaughter and deceit becomes more obvious; economic imperialism will solve our problems in the end, though in a society where Darwin still has vociferous opponents, it may take some time, as Captain Oates said.

So if a political settlement expedites matters even better. I've seen my share of bloody messes, and I'm sick of it. Young lives wasted and ruined, dead faces staring sightless. Fresh blood gleams and newly shed tears glint, but only for a heartbeat. Then the blood clots and turns dull and rusty and the tears dry and disappear.

The wounds still gape, but eventually even they will heal; I just want to forget.
The Principles and Practice of Medicine.
Journal: Annals of Internal Medicine (1972)

Although the familiar format is maintained, one notes that Osler's name no longer appears on the back strip of this sixteenth edition of the famous textbook. The Osler tradition is, however, preserved in an essay by Dr. James G. Carr dealing with the progressive changes in the book from the first edition in 1892 through those compiled by McCrae and by Christian up to the present time. No one could be better fitted to take over the important burden of preparing a textbook than Dr. Christian. He has thoroughly revised and brought up to date all the material in a precise and scholarly way. Space forbids detailed analysis. It may be said, however, that the general method of arrangement and classification used in recent editions is continued. Some of Osler's original descriptions still remain and indeed cannot be surpassed, although such phrases as "among women, anemic, dyspeptic servant girls seem
Rivaroxaban for Treatment of Suspected or Confirmed Heparin-Induced Thrombocytopenia Study
Authors: Lori Ann Linkins, Theodore E. Warkentin, Menaka Pai, Sudeep Shivakumar, Rizwan Manji, Philip S Wells, Cynthia M Wu, Ishac Nazi, Mark A. Crowther
Journal: Blood (2015)
Phase I study of regorafenib (BAY 73-4506), an inhibitor of oncogenic and angiogenic kinases, administered continuously in patients (pts) with advanced refractory non-small cell lung cancer (NSCLC).
Authors: M. S. Kies, G. R. Blumenschein, O. Christensen, T. Lin, A. W. Tolcher
Journal: Journal of Clinical Oncology (2010)

7585 Background: Regorafenib is a novel diphenylurea oral multikinase inhibitor of angiogenic (VEGFR1-3, TIE2), stromal (PDGFR- β, FGFR), and oncogenic kinases (KIT, RET, RAF). In in vivo models, including NSCLC, regorafenib has demonstrated a broad spectrum of antitumor activity. Regorafenib administration (21 days (d) on/7 d off dosing) resulted in a 31% partial response (PR) rate in a Phase II study in patients (pts) with metastatic renal cell cancer. Methods: This phase I study assessed the safety, pharmacokinetics (PK), and efficacy of regorafenib, administered continuously in repeating cycles of 21 d in pts with refractory NSCLC. PK profiles were performed after single dose and in steady state. Tumor response was evaluated by RECIST. Results: Twenty-three pts with progressing NSCLC were treated with regorafenib at doses of 100 mg (n = 22) and 120 mg (n = 1) administered orally once daily. Pts had been exposed to extensive previous treatment (carboplatin, 82%; pemetrexed, 64%; EGFR inhibitors, 64%; docetaxel, 45%; paclitaxel, 45%; bevacizumab, 41%; cisplatin, 14%). Median regorafenib treatment duration was 84 d (range, 12-281). Drug- related adverse events of all grades reported in >20% of pts were hand-foot skin reaction (HFSR) (35%; CTC 3, 13%), extremity pain (30%; CTC 1 only), hypothyroidism (26%; CTC 1-2 only), and rash/desquamation (26%; CTC 1-2 only). The most frequent reason for dose reduction or interruption was skin toxicity, mostly HFSR, occurring in 4 pts. The AUC and Cmax of regorafenib at steady state were 35.04 mg*hr/L and 2.52 mg/L, respectively. Active metabolites M2 and M5 were 45% and 30% of parent AUC at steady state. Of 17 evaluable pts, 13 had stable disease (SD) at least 6 wk after the start of treatment (76%), and 4 had SD for > 12 wk. Four pts had progressive disease in the first tumor assessment (24%). One pt with SD had a PFS of 279 days and a tumor reduction of > 30% in 2 measurements. Conclusions: Regorafenib, dosed continuously at 100 mg, was well tolerated in pts with advanced refractory NSCLC. Promising clinical activity was shown, with a disease control rate (SD) of 76% in evaluable pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Healthcare Pharmaceuticals Bayer Chemotherapy Foundation Bayer
Enlarging Abdominal Mass
Authors: George B. Carter, James W. Tanner
Journal: JAMA (1963)

Dr. Abbott R. Miller: A 68-yr-old male was admitted to the Massachusetts General Hospital with a chief complaint of abdominal pain and fever. For 5 weeks prior to admission he had experienced anorexia, evening chills with fever, and urinary urgency with frequency. For 6 days previous to admission he had generalized hypogastric, inguinal, and scrotal pain, somewhat greater on the left. The past medical history revealed that he had been treated for syphilis 45 yr previously with heavy metals and more recently with penicillin. Bilateral lumbar sympathectomy was performed in 1954 for peripheral vascular insufficiency. Hypertension had been known to be present for years. Examination on admission revealed an obese male with a blood pressure of 230/100 mm Hg and a temperature of 101 F (38.3 C). A grade-2 pansystolic heart murmur was noted and there were a few fine rales in the left lung base. There was slight left
Courses are available
Authors: R G Mann
Journal: BMJ (1995)

and a defibrillator as well as my medical bag up five flights of stairs in a block of flats, where the lift is invariably out of order or its floor swimming in urine?What do I do with the equipment while visiting patients who do not require it?If I leave it in the car the possibility of its being stolen is high.Have the authors considered the practical implications of their advice?
Spread of Human Cytomegalovirus (HCMV) After Infection of Human Hematopoietic Progenitor Cells: Model of HCMV Latency
Authors: T. Zhuravskaya, J.P. Maciejewski, D.M. Netski, E. Bruening, F.R. Mackintosh, S. St Jeor
Journal: Blood (1997)
Case 16-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Donald P. Goldstein, William R. Welch
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of a pulmonary mass.She was well until six years previously, when her first pregnancy terminated in a spontaneous abortion in the first trimester. A daughter was born two years later of a full-term normal delivery. Three years before admission a third pregnancy also ended in a spontaneous abortion in the first trimester; dilatation and curettage was not performed. Her physician stated that she had ovarian cysts that involuted after the administration of an unknown hormone preparation. Eleven months before entry she had marked menometrorrhagia; medroxyprogesterone acetate was . . .
Overexpression of A kinase interacting protein 1 attenuates myocardial ischaemia/reperfusion injury but does not influence heart failure development
Authors: Harmen G. Booij, Hongjuan Yu, Rudolf A. De Boer, Cees W.A. van de Kolk, Bart van de Sluis, Jan M. Van Deursen, Wiek H. Van Gilst, Herman H.W. Silljé, B. Daan Westenbrink
Journal: Cardiovascular Research (2016)

A kinase interacting protein 1 (AKIP1) stimulates physiological growth in cultured cardiomyocytes and attenuates ischaemia/reperfusion (I/R) injury in ex vivo perfused hearts . We aimed to determine whether AKIP1 modulates the cardiac response to acute and chronic cardiac stresses in vivo . Transgenic mice with cardiac-specific overexpression of AKIP1 (AKIP1-TG) were created. AKIP1-TG mice and their wild-type (WT) littermates displayed similar cardiac structure and function. Likewise, cardiac remodelling in response to transverse aortic constriction or permanent coronary artery ligation was identical in AKIP1-TG and WT littermates, as evidenced by serial cardiac magnetic resonance imaging and pressure–volume loop analysis. Histological indices of remodelling, including cardiomyocyte cross-sectional diameter, capillary density, and left ventricular fibrosis were also similar in AKIP1-TG mice and WT littermates. When subjected to 45 min of ischaemia followed by 24 h of reperfusion, AKIP1-TG mice displayed a significant two-fold reduction in myocardial infarct size and reductions in cardiac apoptosis. In contrast to previous reports, AKIP1 did not co-immunoprecipitate with or regulate the activity of the signalling molecules NF-κB, protein kinase A, or AKT. AKIP1 was, however, enriched in cardiac mitochondria and co-immunoprecipitated with a key component of the mitochondrial permeability transition (MPT) pore, ATP synthase. Finally, mitochondria isolated from AKIP1-TG hearts displayed markedly reduced calcium-induced swelling, indicative of reduced MPT pore formation. In contrast to in vitro studies, AKIP1 overexpression does not influence cardiac remodelling in response to chronic cardiac stress . AKIP1 does, however, reduce myocardial I/R injury through stabilization of the MPT pore. These findings suggest that AKIP1 deserves further investigation as a putative treatment target for cardioprotection from I/R injury during acute myocardial infarction.
Markers of apoptosis in cardiovascular tissues focus on Annexin V
Authors: W van Heerde,
Journal: Cardiovascular Research (2000)

In the last decade, apoptosis (or programmed cell death) has become appreciated as an important process in the development of the cardiovascular system. Moreover, apoptosis contributes to the adaptation of the system to the environment. We are at the beginning of understanding its relevance to cardiovascular physiology and pathology. This understanding forms the key to implement apoptosis in diagnosis and therapy of cardiovascular diseases. New avenues for pharmacological intervention are expected to arise from the synergy of our knowledge about the molecular mechanisms of apoptosis, and how apoptosis integrates in the complex environment of the cardiovascular tissue. The latter strongly depends on techniques to measure apoptosis. Currently, we are facing a relative paucity in available techniques, covering both specificity and sensitivity, and furthermore allowing quantitative analysis, preferably in combination with morphology. This field, however, is rapidly evolving and is fed by the expanding knowledge about the molecular mechanisms of apoptosis. In this paper we will briefly review the available techniques to detect and/or quantify apoptosis. These methods are based on the analysis of cellular morphology, either by light- or electron microscopy, DNA fragmentation (TdT-mediated X-dUTP nick end labeling or in situ nick end labeling), or cytoplasmic and membrane changes. Furthermore, the advantages and limitations of these techniques for their use in cardiovascular research will be outlined. In the text we will refer to available reviews and protocols which discuss the techniques in more detail. The main part of this article will, however, focus on a recently introduced technique, the Annexin V-based apoptosis detection assay. The principle, characteristics, pro's and contra's of this new apoptosis detection assay will be discussed.
HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy
Authors: Tzu-yin Lin, Wenchang Guo, Qilai Long, Aihong Ma, Qiangqiang Liu, Hongyong Zhang, Yee Huang, Siddarth Chandrasekaran, Chongxian Pan, Kit S. Lam, Yuanpei Li
Journal: Theranostics (2016)

Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity.In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer.This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal-and photodynamic-therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy.Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft.This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.
Craving for Alcohol in Sober Alcoholics
Authors: Roy J. Mathew, James L. Claghorn, John Largen
Journal: American Journal of Psychiatry (1979)

The craving for alcohol experienced by 46 abstinent alcoholics was investigated with a structured interview, a personality inventory (the neuroticism Scale Questionnaire), and a mood state adjective checklist (Profile of Mood States). It was found that craving is a continuum, not an all-or-none phenomenon. The intensity of craving was positively correlated with the trait anxiety of the subject and inversely correlated with the duration of abstinence from alcohol. A large proportion of the craving was precipitated by environmental factors and relieved by psychological methods. A variety of mood changes accompanied carving. Only one mood state, anger-hostility, significantly differentiated subjects who experienced mild craving from those reporting severe craving.
Doctor Women
Authors: Franz J. Ingelfinger
Journal: New England Journal of Medicine (1974)

Some years ago, Dr. Estelle Ramey, Professor of Physiology at Georgetown and articulate feminist (she helped to harry off the market that textbook which illustrated anatomy with Playboy-type bodies), engaged in the following exchange: Question: Don't you think that attitudes toward women in the medical sciences are changing rapidly? Answer: (by Dr. Ramey) No. Cultural biases never change rapidly. Stereotypes are bred in the bone of a society and the stereotype of a woman doctor is a horse-faced, flat-chested female in supphose who sublimates her sex starvation in a passionate embrace of the New England Journal of Medicine...1 The . . .
LG-13SECOND-LINE TREATMENT FOR PEDIATRIC LOW GRADE GLIOMA (LGG) - EXPERIENCES FROM THE GERMAN AND SWISS SIOP-LGG-2004 COHORT
Authors: Daniela Kandels, René Schmidt, Sabine Breitmoser-Greiner, Astrid K. Gnekow
Journal: Neuro-Oncology (2016)

LG-13. SECOND-LINE TREATMENT FOR PEDIATRIC LOW GRADE GLIOMA (LGG) EXPERIENCES FROM THE GERMAN AND SWISS SIOP-LGG-2004 COHORT Daniela Kandels1, Rene Schmidt2, Sabine Breitmoser-Greiner1, and Astrid K. Gnekow1; Children’s Hospital, Klinikum Augsburg, 86156 Augsburg, Germany; Institute of Biostatistics and Clinical Research, University of Muenster, 48149 Muenster, Germany OBJECTIVE: Though chemo(CT) and radiotherapy (RT) are effective for non-resectable pediatric LGG, progression following first non-surgical treatment is frequent. Wereport results for salvage-therapy of events after first nonsurgical treatment.METHODSAND RESULTS: 180 events followed primary treatment in the SIOP-LGG-2004-trial (30/169 RT [2/10 NF1]; 150/321 CT [37/124 NF1]), median follow-up (FU) since start of first therapy: 6.9 years. 54/150 events occurred during chemotherapy (early, 18/54 died), 96/150 after termination (median time to progression: 3.0 years, 5/96 died). Second-line-radiotherapy: 3/30 RT-, 43/150 CT-patients. Second-line-chemotherapy: 14/30 RT-, 70/150 CT-patients. Followingmultiple progressions 3 or more lines of rescue-therapy were applied in 7/30 RT-, 46/150 CT-patients. Vincristin/cisplatin/cyclophosphamide (VCR/Cis/Cyc, n 1⁄4 25), vincristin/carboplatin (VCR/Carb, n 1⁄4 25), vinblastine (VBL, n 1⁄4 19) and temozolomide (TMZ, n 1⁄4 8) were used most commonly as second-line chemotherapy. Median time to next progression varied between drugs: VCR/Carb 2.4 years (median FU 3.5 years), VCR/Cis/Cyc 1.9 years (median FU 6.6 years), VBL 1.1 years (median FU 1.5 years), TMZ 0.9 years (median FU 4.4 years). 30/180 patients died. Three-years-overall-survival since first event after start of first therapy differed for patients with vs. without dissemination (75.0% vs. 88.2%, p 1⁄4 0.043), diffuse glioma WHO-grade II vs. other histologies (61.5% vs. 86.6%, p 1⁄4 0.018), with a trend for caudal-brainstem-site vs. other localization (73.8% vs. 86.8%, p 1⁄4 0.105). CONCLUSION: Although progression of non-resectable LGG is frequent following first-line therapy, patients can be salvaged by subsequent treatment(s). Second progression-free survival is longer following platinumbased chemotherapy. Impaired survival after first treatment-failure seems to be associated with dissemination, diffuse histology, caudal-brainstem-site and early events. Standardized second-line treatment-protocols are required. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.13 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.