tbuckley/cabot-search huggingface dataset:
Lymph node micro-architecture can be imaged using optical coherence tomography.
Authors: RA McLaughlin, L Scolaro, BR Klyen, S Hamza, P Robbins, C Saunders, DD Sampson
Journal: Cancer Research (2009)

Abstract Abstract #804 Background: Histological assessment is the gold standard technique for identification of lymph node involvement in breast cancer. However, this may only be performed ex vivo and will often result in the unnecessary excision of healthy lymph nodes. In axillary clearance, this will result in lymphedema in approximately 26% of patients. Optical Coherence Tomography (OCT) is a real-time imaging modality with the potential to perform in vivo optical biopsy of lymph nodes. We undertook ex vivo imaging of excised lymph nodes to identify which aspects of the lymph node micro-architecture could be imaged using OCT, and to identify differences between cancerous and normal nodes.&amp;#x2028; Materials and Methods: 18 lymph nodes were taken from 13 patients undergoing axillary clearance or sentinel lymph node biopsy. Fresh excised lymph tissue was dissected into 2mm slices. A 3D-OCT scan was acquired, with a resolution of ∼11μm in both axial and lateral dimensions. Each sample underwent subsequent histological analysis using Haematoxylin and Eosin (H&amp;E) staining and matched against the 3D-OCT data sets.&amp;#x2028; Results: OCT images demonstrated differentiation of the three major tissue types found in the lymph node: adipose, lymph cortex and lymph capsule. Adipocytes demonstrated a characteristic honeycomb structure that was also visible in H&amp;E stained histology. The cortex, containing a high concentration of lymphocytes, was found to give a strong level of optical backscatter in the OCT image. The capsule, consisting of less dense stroma tissue, could generally be differentiated from the cortex. Small blood vessels in the stroma and cortex presented as areas of low backscatter. Sinuses were identified as contributing to variation in intensity within the cortex. Germinal centers could be distinguished from resting lymphoid tissue by a characteristic circular structure apparent in both OCT and histology. Cancerous regions were found to be devoid of these characteristic micro-architectural structures, as the malignant cells replaced normal lymph tissue. Figure 1 shows the H&amp;E histology image and corresponding OCT scan of a normal lymph node. Adipose, cortex, stroma and small blood vessels are all apparent in this sample.&amp;#x2028; Discussion: These results demonstrate that OCT is able to differentiate relevant structures within lymph nodes. Our findings suggest that lymph node metastasis is evident by the lack of these structures. This corresponds well with histological findings. This work forms a basis for future in vivo studies aimed at assessing lymph node involvement prior to excision.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 804.
Life or Death
Authors: Thomas G. Peters
Journal: JAMA (1991)

IN 1989, 1878 people died while awaiting organ transplantation. Public awareness programs, professional education, and legislation have not increased organ donation; the motive for consent in organ donation remains altruism. I shall argue that because of an ever larger number of patients listed as candidates for lifesaving organs, the policy of a death benefit payment to motivate families of potential organ donors should be studied. A death benefit of $1000 paid through organ procurement organizations would not necessarily be coercive. Laws now prohibiting organ brokerage and assuring fair organ allocation would continue unchanged. A death benefit payment may most favorably affect the socially disenfranchised through increased organ transplantation in minority populations. Because so many salvageable lives are now lost, only because organs cannot be obtained, pilot programs to determine the impact of death benefit payment to the enabling (consenting) next-of-kin should be initiated. If organ recovery increases sufficiently, a nationwide
Abstract 663: The comparative efficacy of the PARP inhibitors AG14361, ABT888 and AZD2281 in the treatment of triple negative and BRCA1 breast cancer
Authors: Tatiana Velikodvorskaya, Naheed Fatima, Renee Quick Fountain, Joseph A. De Soto
Journal: Cancer Research (2010)

Abstract Introduction: Most preclinical studies have used “in vitro” animal cell lines, “in vivo” allografts and/or gene knockdowns to predict the clinical efficacy of PARP1 and PARP1 &amp; 2 inhibitors in the treatment of human breast cancer. It has been shown however that “in vitro” experiments with human breast cancer cell lines are more useful in predicting the clinical performance of cancer drugs than these other methods. In this study, the PARP1 inhibitor AG14361 and the PARP1 &amp; 2 inhibitors AZD2281 and ABT888 were tested against a panel of 25 human breast cancer cell lines. Methods: The MTT assay was used to determine the IC50 inhibitory effect of the PARP inhibitors against the human breast cancer cell lines over a 72 hour period with each experiment being replicated at least 10 times. The MTT assay was validated for each cell line using direct counting via hemacytometer &amp; trypan blue staining. Human to mouse xenografts were then challenged by PARP inhibitors. The IC50 results were then correlated with the PARP activity of each cell line. Results: The PARP1 inhibitor AG14361 was 5 and 8 fold more effective in inhibiting human breast cancer growth than ABT888 and AZD2281 respectively. The average IC50 values for AG14361, ABT888 and AZD2281 against BRCA1-/- human breast cancer cell lines were 20, 120, and 190 micromolar respectively. The average IC50 values for non-BRCA1 triple negative breast cancer were 24, 110 and 165 micromolar respectively. ANOVA analysis sustained the null hypothesis between BRCA1-/- breast cancer and non-BRCA1 triple negative breast cancer. Xenograft studies mirrored the “in vitro results”. These IC50 values are significantly higher than previously published preclinical data that utilized BRCA1 -/- animal cell lines and human BRCA1 gene knockdowns. This suggests that BRCA1 animal cell lines are more sensitive to PARP1 inhibitors and that human BRCA1 -/- gene knockdowns may be fundamentally different from naturally derived BRCA1-/- breast cancer cell lines. Conclusion: The PARP1 inhibitor was more effective than the PARP1 &amp; 2 inhibitors in inhibiting breast cancer growth. Non-BRCA1 triple negative breast cancers were at least as sensitive to PARP inhibition as BRCA1 breast cancers. 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 663.
Abstract IA10: Li-Fraumeni syndrome: p53 and beyond
Authors: Jonathan Wasserman, Anita Villani, Nardin Samuel, Diana Merino, Ana Novokmet, Margaret Pienkowska, Badr IdSaid, David Malkin
Journal: Cancer Research (2014)

Abstract Germline TP53 mutations are observed in ∼80% of patients with Li-Fraumeni syndrome (LFS) and a lesser frequency of patients meeting the revised Chompret criteria. A variety of studies are being conducted exploring the role of genetic modifiers on p53 function and their impact in refining the genotype:phenotype correlation of the TP53:LFS relationship. In this presentation, four classical pediatric-onset LFS tumors (choroid plexus carcinoma, medulloblastoma, adrenocortical carcinoma and rhabdomyosarcoma) will be used as examples to demonstrate the molecular nuances of this complex relationship. A spectrum of findings will be outlined that support the notion that presence of a germline TP53 mutation in the context of different modifying effects of intragenic TP53 polymorphism as well as variants in genes and proteins that play important roles in the p53 network confers certain biological features to the presentation of these tumors. Biological mechanisms will be discussed and strategies for early cancer detection will be presented. Citation Format: Jonathan Wasserman, Anita Villani, Nardin Samuel, Diana Merino, Ana Novokmet, Margaret Pienkowska, Badr IdSaid, David Malkin. Li-Fraumeni syndrome: p53 and beyond. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA10. doi:10.1158/1538-7445.CANSUSC14-IA10
Occupational asthma in a coal miner.
Authors: P. M. Gamboa, I. Jauregui, I. Urrutia, I. Antepara, G. Gonzalez, V. Mugica
Journal: Thorax (1996)

Occupational asthma in coal miners is hardly recognised. A report is presented of a coal miner whose clinical picture suggested a respiratory allergy which occurred only in the mine where he worked. Serum specific IgE levels, skin tests, and bronchial provocation tests with different commercial extracts showed sensitisation to Rhizopus nigricans. Rhizopus spp were found inside the mine, as demonstrated by cultures on petri plates.
Vital Statistics of the War.
Authors: J. F. Walsh
Journal: JAMA (1898)

Camden, N. J., Nov. 16, 1898. <h3>To the Editor:</h3> —Dr. Charles Smart of the U. S. A., in a letter directed to you, of the date of October 22, complains of an editorial which appeared in the<i>Philadelphia Medical Journal</i>relative to the mortality in the Spanish war, and causes of the mortality. What he says is all very well for the most part; but will he explain why so many soldiers not exposed to the hardships of war, but quartered in a country rich and resourceful in every way, died of disease. When we consider that these same soldiers had all undergone strict physical examination and been pronounced of excellent resisting power, the mortality among them seems to indicate gross incapacity somewhere. Suppose that during the Civil War proportionately as large a number of soldiers had been isolated from the scene of actual warfare and that the same percentage
Resistance Mechanisms in Staphylococcus aureus
Authors: STEPHEN J. SELIGMAN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 December 1982Resistance Mechanisms in Staphylococcus aureusSTEPHEN J. SELIGMAN, M.D.STEPHEN J. SELIGMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-6-931_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article by Sabath (1) contains an excellent description of resistance mechanisms to the beta-lactam antibiotics inStaphylococcus aureusthat relate to beta-lactamase activity and to tolerance. It should be pointed out, however, that there is an alternative method of describing mechanisms associated with intrinsic resistance. Methicillin-resistantS. aureus(2) in common with methicillin-sensitive strains (3) produce resistant mutants. The mutants are slower growing than the parent strain and these "small colony variants" may take several days to produce colonies on agar. What distinguishes the vast majority of methicillin-resistant strains is that the average organism (that is,...References1. SABATH L. Mechanisms of resistance to beta-lactam antibiotics in strains of Staphylococcus aureus. Ann Intern Med. 1982;97:339-44. LinkGoogle Scholar2. SELIGMAN S. Methicillin-resistant staphylococci: genetics of the minority population. J Gen Microbiol. 1966;42:315-22. CrossrefMedlineGoogle Scholar3. DEMEREC M Production of staphylococcus strains resistant to various concentrations of penicillin. Proc Natl Acad Sci. (USA) 1945;31:16-24. CrossrefMedlineGoogle Scholar4. HARTMANTOMASZ BA. Altered penicillin-binding proteins in methicillin-resistant strains of Staphylococcus aureus. Antimicrob Agents Chemother. 1981;19:726-35. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Downstate Medical Center Brooklyn, NY 11203 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOxidation 1 December 1982Volume 97, Issue 6Page: 931-932KeywordsAntibioticsStaphylococcus aureus Issue Published: 1 December 1982 PDF downloadLoading ...
Effect of intracoronary CO2 gas injection on myocardial blood flow
Authors: S.-M. LIU, C. S. ALEXANDER
Journal: Cardiovascular Research (1972)

Intracoronary injection of 5 ml. CO2 gas in 11 anaesthetized dogs caused marked coronary vasodilatation and enhanced myocardial blood flow both during control ventilation and when preceded by a brief period of moderate hypocapnia. It caused no tachyarrhythmia or change in mean aortic pressure. On the other hand, O2 gas injection caused ventricular fibrillation leading to death in two of the three animals studied.
Eicosapentaenoic Acid: The Answers Are Not All In
Authors: Mellar P. Davis
Journal: Journal of Clinical Oncology (2005)

TO THE EDITOR: Jatoi et al should be congratulated in successfully performing a study comparing eicosapentaenoic acid (EPA) supplements versus megestrol acidate versus both for patients with cancer-associated wasting. The trial involved 421 patients who received EPA supplements twice a day (placebo v megestrol 600 mg per day or 2-gram EPA-containing supplements v both). The EPA arm, either alone or in combination, was found not to improve appetite or weight compared with megestrol alone. However, there are several questions surrounding the design of the trial. Weight gain may not be the best outcome to measure for either anorexia or cachexia; rather, lean body mass as measured by bioelectric impedance and functional status are more relevant outcomes. Secondly, measurement of drug absorption by plasma, red cell, or leukocyte levels of EPA would have improved the reliability of this study. It is known that a significant number of patients will take EPA off study and a certain subset of patients will not absorb EPA. Compliance and absorption factors would have influenced the results of this study. In a study by Fearon et al, a significant portion of patients had taken undisclosed EPA supplements and one fourth of patients randomly assigned to EPA did not have increases in plasma EPA. This study demonstrated significant weight stabilization and increased lean body mass correlated with plasma EPA levels. Abnormal digestive function and malabsorption are commonly seen in cancer-associated anorexia and cachexia, which influences EPA bioavailabilty. Jatoi et al evaluated response at 4 weeks. However, the benefits of EPA found by Fearon et al occurred at 8 weeks. Previous dose finding studies have demonstrated that patients tolerate higher doses of EPA when given alone. Burns et al performed a dose-finding study through the Cancer and Leukemia Group B (study 9473) and found that a dose of 0.3 g/kg per day of EPA plus decosahexaenoic acid was the maximum tolerable dose. Barber and Fearon found patients could tolerate doses as high as 18 grams of EPA per day (range, 9 to 27 grams). It may be premature to end the ongoing interest in omega-3 fatty acids. A better trial design perhaps would include a high-dose omega-3 fatty acid without nutritional supplement megestrol acetate arm to the study. Drug tolerance, weight, functional status, bioelectric impedance for lean body mass, and plasma or red cell EPA levels would help clarify potential confounding factors. This would require testing omega-3 fatty acid without nutritional supplements because it appears that EPA supplements are not well tolerated by patients and thus have a dose ceiling. It would be important to test maximum tolerable doses as demonstrated by the Cancer and Leukemia Group B study before declaring that EPA does not improve weight, appetite, or lean body mass and is not better than, nor adds to, megestrol acetate benefits.
288Termination of reentrant tachyarrhythmias by light: from electroshock towards shockless cardioversion by cardiac optogenetics
Authors: B O Bingen, MC Engels, Z Neshati, I Feola, DL Ypey, AV Panfilov, SFA Askar, MJ Schalij, DA Pijnappels, AAF De Vries
Journal: Cardiovascular Research (2014)

Purpose: Atrial Fibrillation (AF) is the most common cardiac rhythm disorder of clinical significance. Electric cardioversions remain the mainstay of treatment in symptomatic AF-patients. However, the used electroshocks result in severe discomfort and tissue damage, which necessitate anaesthesia and preclude the use of implantable devices in AF. Hypothetically, forced expression of light-gated cation-channels in cardiomyocytes and subsequent activation (optogenenetics), might deliver the depolarizing force sufficient for cardioversion, circumventing aforementioned drawbacks of electroshocks. Therefore, we investigated the feasibility of optogenetics in the termination of spiral wave reentry -a mechanism underlying fast activation during AF- and compared it to conventional electrotherapy. Methods: Neonatal rat atrial cardiomyocyte monolayers were transduced with lentiviral vectors encoding the calcium-translocating channelrhodopsin (CatCh↑) or eYFP as control (eYFP↑), and burst-paced to induce fibrillation based on spiral wave reentry. Effects of optogenetic light-therapy on reentry were investigated using optical and micro-electrode array mapping (MEA) techniques. Westernblot and immunocytology were used to confirm CatCh and eYFP expression. Results: Pulsed blue light (10 ms/470 nm) elicited action potentials in cultures transduced with CatCh↑ but not eYFP↑, confirming functional CatCh-mediated photocurrent. Reentry was terminated by a 500-ms light pulse in 100% CatCh↑ (n=35) vs 0% (n=11) in eYFP↑-transduced atrial cultures. Mechanistically, uniform depolarization by CatCh-activation resulted in decreased excitability of the fibrillating monolayer (MEA peak-to-peak amplitude decreased 304.5±254 vs 12.6±11.5 μV in eYFP↑). This caused an increase in the coresize of functional reentry and phase-singularity (PS) drift, which increased the chance of PS-PS or PS-boundary collisions, leading to reentry termination. In comparison, electrical reentry termination could be achieved only with 10 ms shocks of 60.5±15V. Conclusions: For the first time it is shown that reentry can be terminated effectively by using tissue-endogenous depolarizing currents triggered by light, using energy levels well below pain threshold, in contrast to electroshock therapy in our model. This approach can potentially circumvent the necessity of electroshocks for cardioversion. Hence this study provides a new rationale for the design of shockless/painfree anti-fibrillatory treatment strategies.
Impact of hepatitis C triple therapy availability upon the number of patients to be treated and associated costs in France: a model-based analysis
Authors: Sylvie Deuffic-Burban, Philippe Mathurin, Stanislas Pol, Christine Larsen, Françoise Roudot-Thoraval, Jean Claude Desenclos, Daniel Dhumeaux, Yazdan Yazdanpanah
Journal: Gut (2011)

<h3>Objective</h3> The combination of pegylated interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor (PI) has been approved in summer 2011 for the treatment of genotype 1 (G1) hepatitis C virus (HCV)-infected patients, with a substantially improved efficacy. The aim of this study was to estimate the number of G1 patients to be treated in France in 2012 and associated costs. <h3>Methods</h3> A published model of HCV and data on PEG-IFN sales were used to estimate patients needing treatment using three scenarios. (1) HCV screening rate unchanged versus 2010; proportion of treated F0–F1 patients unchanged, proportion of treated F2–F4 patients increased to the current proportion of treated F2–F4 G2/3 patients. (2) Scenario 1 but the proportion of treated F0–F1 patients increased to the current proportion of treated F0–F1 G2/3 patients. (3) Scenario 2 but a 5% increase in the HCV screening rate. To estimate cost, treatment duration was multiplied by drug unit cost. Probabilities corresponding to treatment duration were estimated based on liver fibrosis stage, treatment-naive or experienced status of the patient and virological response kinetics on treatment. <h3>Results</h3> Compared with the 5100 G1 patients treated in 2010, the number of G1 patients receiving treatment in 2012 would be 15 000 in scenario 1, 18 300 in scenario 2 and 19 400 in scenario 3, among whom 2.5–3.7% may receive PEG-IFN/RBV and 96.3–97.5% PEG-IFN/RBV+PI. Costs associated with this regimen use ranged from 497 to 638 million Euros. <h3>Conclusion</h3> These model-based estimates indicate that new anti-HCV treatments may result in a three- to fourfold increase in the number of G1 patients to be treated in France in 2012.
Chromosome aberrations in workers exposed to arsenic.
Authors: G Beckman, L Beckman, I Nordenson
Journal: Environmental Health Perspectives (1977)

The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Rönnskär smeltery in northern Sweden. In the smelter workers, 87 aberrations were found in 819 mitoses. The number of aberrations varied individually from 0 to 25 aberrations per 100 cells. In a control material 13 aberrations were found in 1012 mitoses. The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty.
LHRH: Clinical applications growing
Authors: Terra Ziporyn
Journal: JAMA (1985)

Barely 13 years after its initial discovery, the hypothalamic luteinizing-hormone releasing hormone (LHRH) appears to be claiming a large territory in clinical medicine. "There's almost no subspecialty of medicine that will be left untouched by the [research] advances associated with LHRH or its analogues," predicts William F. Crowley, MD, associate professor of medicine at Harvard University Medical School, Boston. He points out that this polypeptide hormone (also known as gonadotropin-releasing hormone or GnRH) is already providing new treatments for several human diseases and "represents one of the examples where an investment in basic science has profound clinical applications." Crowley, who is also chief of reproductive endocrinology at the Massachusetts General Hospital in Boston, discussed the therapeutic implications of LHRH and its analogues at the Seventh International Congress of Endocrinology in Quebec City. So far, he says, the ability of LHRH to either stimulate or suppress reproductive processes has been applied
Impact of Heterogeneity of Human Peripheral Blood Monocyte Subsets on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction
Authors: Hiroto Tsujioka, Toshio Imanishi, Hideyuki Ikejima, Akio Kuroi, Shigeho Takarada, Takashi Tanimoto, Hironori Kitabata, Keishi Okochi, Yu Arita, Kohei Ishibashi, Kenichi Komukai, Hideaki Kataiwa, Nobuo Nakamura, Kumiko Hirata, Atsuhsi Tanaka, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2009)
Efficacy and Safety Of a New Olopatadine Hydrochloride, 0.77% Ophthalmic Formulation In Patients With Allergic Conjunctivitis Using The Conjunctival Allergen Challenge (CAC) Model (NCT01479374)
Authors: Gail Torkildsen, Thomas Macejko, Abhijit Narvekar, Mark Bergmann
Journal: Journal of Allergy and Clinical Immunology (2014)
475 Sustained virological response (SVR) to peginterferon alfa-2A (40KD) (PEGASYS) plus ribavirin (RBV) and amantadine (AMA) vs induction therapy with interferon alfa-2A (Roferon-A) plus RBV and AMA in IFN/RBV non responders (NR) with chronic hepatitis C (CHC)
Authors: S. Fargion, M. Borzio, A. Maraschi, A. Cargnel
Journal: Journal of Hepatology (2004)