tbuckley/cabot-search huggingface dataset:
One Hour Hepatic Ischemia Without Serious Damage
Authors: Louis F. Anastasia
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Since an aggressive surgical approach to resection of major portions of the liver for massive trauma or tumor is currently being suggested<sup>1</sup>and liver transplant is being evaluated, the length of time that hepatic ischemia can be effected without permanent damage has increasing significance. Our case is reported because it offers one observation on this point. <h3>Report of a Case:—</h3> A 33-year-old woman with previously demonstrated cholelithiasis was found to have acute cholecystitis, a normal-sized common duct, and a normal liver. As the cystic artery was being dissected, there was sudden severe arterial hemorrhage. Immediate control with finger compression through the foramen of Winslow was accomplished. At 10:09 AM a vascular clamp was placed across the portal triad, with complete control of bleeding. The common hepatic artery was identified and individually clamped in approximately one-half hour, at which time the clamp was removed from the porta
Case 16-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Charles A. Sanders, Austin L. Vickery
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 39-year-old man was admitted to the hospital because of congestive heart failure.He was known to have a heart murmur since his high-school days but had always been well and vigorous, engaging in calisthenics and jogging. Six months before admission he awoke with anterior chest pain and extreme fatigue and remained in bed all day. There were no further episodes of chest pain, but the fatigue persisted during the next few months, and he occasionally felt his heart beating irregularly. Six weeks before entry he was admitted to another hospital, where an ultrasound study of the . . .
Abstract 2115: A chemicogenetic interrogation of colorectal cancer identifies a shared chemical vulnerability in Wnt signaling and telomere length maintenance.
Authors: Ozlem Kulak, Brody Holohan, Xiaofeng Wu, Lawrence Lum
Journal: Cancer Research (2013)

Abstract Despite the general acceptance that loss of the APC tumor suppressor is the predominant cancer-initiating event in colorectal cancer (CRC), a therapeutic strategy premised upon disabling deviant gene transcription associated with this phenomenon currently does not exist. Chemical antagonism of the poly-ADP ribosylase enzymes Tankyrase 1 and 2 (Tnks1&amp;2) results in the destruction of the transcriptional co-activator β-catenin by promoting the stability of a β-catenin destruction complex. We have evaluated the consequences of disrupting β-catenin activity on the CRC signaling network using faithful reporters of the most frequently corrupted cellular processes (Wnt/β-catenin, p53, and Kras signaling), and a portfolio of Tnks inhibitors identified from a chemical library screen. In addition to inducing loss of β-catenin activity, the exposure of cells to Tnks inhibitors resulted in increased p53 activity. We demonstrated that this unexpected cellular response is due to loss of Tnks ability to regulate the shelterin complex that protects the telomeric sequences found at the ends of chromosomes. Long term culturing of cancerous cells with Tnks inhibitors resulted in telomere shortening and cellular senescence. Our findings reveal a single agent strategy for targeting two cellular processes that support the renewal of cancer initiating cells - Wnt signaling and telomere length maintenance. Citation Format: Ozlem Kulak, Brody Holohan, Xiaofeng Wu, Lawrence Lum. A chemicogenetic interrogation of colorectal cancer identifies a shared chemical vulnerability in Wnt signaling and telomere length maintenance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2115. doi:10.1158/1538-7445.AM2013-2115
The Ribonucleoside Analog, 8-Chloro-Adenosine, Inhibits the mTOR Pathway and Induces Autophagy.
Authors: C. Stellrecht, S. Shentu, V. Gandhi, V. Gandhi
Journal: Cancer Research (2009)

Abstract In contrast to deoxyribose or arabinose containing nucleoside analogs that are currently established for cancer therapeutics, 8-chloro-adenosine (8-Cl-Ado) possesses a ribose sugar. This unique nucleoside analog is RNA directed and is in a phase I clinical trial for hematological malignancies. Preclinically, it has been also found to be cytotoxic to a number of epithelial and neuronal cell lines. Previously, we demonstrated that in the breast cancer cell lines, MCF-7 and BT-474, 8-Cl-Ado accumulates as a triphosphate reaching its plateau by 6 h of treatment with 10 μM 8-Cl-Ado. This accumulation was coupled with a parallel decrease in the level of the endogenous ATP pool by 60 and 40%. These changes in nucleoside levels then lead to ∼50% inhibition of RNA synthesis. The net effect of these metabolic changes results in a growth inhibition of ∼90% after 5 d treatment with 10 μM 8-Cl-Ado as measured by MTS assay. This growth inhibition was not due to a cell cycle arrest. Additionally, flow cytometry analysis of annexin V staining showed only a modest induction of apoptosis first detected within 24 h of treatment and reached ∼30% by 5 d. Because the low level of apoptosis can not account for high percent of growth inhibition suggests alternative mechanism(s) for the cytotoxic activity of 8-Cl-Ado. Depletion of the cellular ATP pool is often associated with the activation of AMP-activated protein kinase (AMPK) through its phosphorylation on Thr172. Correspondingly, we demonstrated that 8-Cl-Ado treatment of MCF-7 and BT-474 cells induced AMPK Thr172 phosphorylation within 7 h. Once activated, AMPK alters various energy regulating signaling cascades which includes the mTOR pathway. Inhibition of mTOR leads to a decrease of energy depletion by reducing protein translation and promotes nutrient restoration through the induction of autophagy. 8-Cl-Ado treatment of MCF-7 and BT-474 cells was associated with a decrease in the phosphorylation of the mTOR translation targets, 4E-BP1 and p70S6K within 8 h of treatment. Likewise, there was an increase in the conversion of microtubule-associated protein 1 light chain 3B (LC3B)-I to its lipidated form, LC3B-II, which is an autophagosome marker. Consistent with the immunoblot analysis, fluorescence microscopic analysis of 8-Cl-Ado-treated MCF-7 cells and BT-474 cells expressing a GFP-LC3 construct also demonstrated an increase in the formation of autophagosomes. Finally, acridine orange staining of 8-Cl-Ado treated MCF-7 and BT-474 cells demonstrated the formation autophagolysosomes. This was further confirmed in MCF-7 cells by monodansylcadaverine staining. In conclusion, our data indicates that 8-Cl-Ado treatment induces autophagy in breast cancer cells which in part elicits its growth inhibitory effects on these cells. Based on this biological activity, we are planning to test 8-Cl-Ado in the clinic for patients with breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6116.
Abstract 951: Preclinical evaluation of Xanthohumol in carcinoid cancer growth in vitro and in vivo
Authors: Muthusamy Kunnimalaiyaan, Mary Ndiaye, Catherine M. McManus, Nicole L. Seiler, April Harrison, Herbert Chen
Journal: Cancer Research (2012)

Abstract Background: Besides surgery, there is no potential curative treatment for carcinoid tumors. Because these cancers are metastatic in nature and produce excessive amounts of various bioactive hormones, patients diagnosed with this malignancy will have poor quality of life due to carcinoid syndrome. Therefore, new anticarcinogenic agents are required to improve the effectiveness of treatment. Xanthohumol (XN) (Tetrahydroxy-3′-prenylchalcone) is a prenylated chalconoid found in hops and beer that has been found to have potential anticancer and bioactive properties. Therefore, the purpose of this study was to evaluate the effectiveness of xanthohumol (XN) on carcinoid cancer growth in vitro and in vivo. Methods: To examine the anticancer activity of XN, we treated human gastrointestinal carcinoid BON and bronchopulmonary carcinoid H727 cells with up to 15 μmol/L of XN or carrier (DMSO), and analyzed the effect on cell growth by colony formation assay. The mechanism of growth inhibition was examined by flow cytometry and western analysis for the levels of pro-apoptotic and cell cycle regulatory proteins. To examine the anticancer activity of XN in vivo, subcutaneous BON carcinoid tumors developed in murine xenografts were subjected to intraperitoneal injections of XN (3 mg/kg bwt) or an appropriate volume of DMSO carrier every other day. Results: Treatment with xanthohumol significantly reduced the ability of carcinoid cells to form colonies in a dose-dependent manner. Flow cytometry and western analysis confirmed the observed decrease in cell viability, and showed the decrease was mediated through apoptosis. The carcinoid tumors in the mouse xenograft experiment showed a significant reduction in growth. Conclusions: XN treatment reduced cell viability, colony forming ability and increased cell death through apoptosis. In addition, administration of XN suppressed cancer cell growth in an in vivo xenograft mouse model. Our findings demonstrate for the first time the anti-proliferative effects of xanthohumol in carcinoid cell lines in vivo. Xanthohumol is already being used as a dietary supplement to encourage overall health and has shown few side effects. This fact combined with the potential anticarcinogenic activity found here warrants clinical investigation on patients with carcinoid disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 951. doi:1538-7445.AM2012-951
Thyroid Failure in the Elderly
Authors: Joel I. Hamburger
Journal: JAMA (1987)

To the Editor.—  The article by Rosenthal et al 1 adds in a small way to our understanding of the natural history of noniatrogenic hypothyroidism. Questions of clinical judgment in the design, execution, and editorial evaluation of their study deserve consideration.  Although their patient evaluation included physical examination, only laboratory test data are analyzed. In this perspective the absence of thyrotropinreleasing hormone (TRH) testing is remarkable. One cannot conclude that the presence of a slight elevation in a baseline serum thyrotropin (thyroid-stimulating hormone [TSH]) value necessarily means there will be an increased response to TRH. It is possible that TRH testing might have provided a more sensitive prognostic indicator than microsomal antibody testing.  Current infatuation with laboratory testing aside, simple clinical indexes should not be ignored. In mild noniatrogenic hypothyroidism where sustained TSH level elevations attempt to compensate for falling thyroidal output, usually there is goiter. 2 Hence, the presence
Lip verrucous carcinoma in a pregnant woman successfully treated with carbon dioxide laser surgery
Authors: C.K. Hsu, J.Y.Y. Lee, C.H. Yu, M.M.L. Hsu, T.W. Wong
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Verrucous carcinoma is an uncommon tumour composed of four subtypes according to the site of occurrence: oral type (oral florid papillomatosis) or Ackerman's tumour, anogenital type (Buschke–Löwenstein tumour), plantar type (epithelioma cuniculatum), and other cutaneous sites.1 Oral type verrucous carcinoma (OVC) usually progresses slowly with a low incidence of metastases. The risk factors for OVC include chronic inflammation or irritation, betel nut chewing, smoking, and human papillomavirus (HPV) infection. OVC appears to be very rare during pregnancy. We found no report in a Medline search. We report a 34‐year‐old pregnant woman with OVC. The patient presented at 16 weeks of pregnancy with a 3‐month history of an enlarging verrucous tumour at her lower lip (Fig. 1a). The tumour grew rapidly to a 1·5 × 1·8 × 0·9 cm (141% increase) warty fungating mass in 7 weeks (Fig. 1b). Our plan was to treat the tumour with photodynamic therapy (PDT) after debulking the tumour with carbon dioxide (CO2) laser.2, 3 CO2 laser treatment (model LX‐20; Luxar Corp., Bothell, WA, U.S.A.) was performed after tumescent local anaesthesia with lidocaine 0·2% and adrenaline 1 : 1 000 000. The laser was focused (spot size 0·1–0·2 mm) with the hand‐piece held 1–2 cm from the surgical plane for excision of the main portion of the tumour with a setting of continuous mode at a power level of 7 W. Thereafter, the hand‐piece was held about 10 cm from the skin surface in defocused mode (spot size around 1·0–2·0 mm) for vaporizing the remnants and for coagulation.4 An extended 5‐mm safety margin was evaporated to eradicate the possible lateral spread of the tumour. A thick crust formed after the treatment (Fig. 1c). The wound completely re‐epithelialized in 10 days without sign of residual tumour.
Adolescent Pregnancy Revisited
Authors: Jonathan E. Fielding
Journal: New England Journal of Medicine (1978)

The proportion of teenage births to the total births in the U.S. has increased in recent years. Births are increasing particularly among the younger teenagers. This trend would be even more marked if it were not for the recent liberalization of legal abortions and the increased availability of contraception to teenagers. Despite wide use of abortion among teenage girls, the U.S. still ranks very high in terms of birthrates among females 15-19 years old in comparison with other Western countries. The following 3 problems are associated with teenage pregnancy: 1) increased health risk to the mother; 2) increased health risk to the baby; and 3) social and economic disadvantages, e.g., lost educational opportunities, unstable marriages, and financial problems. Recent surveys have shown that, while sexual activity among teenagers is increasing, contraceptive use is not. The best strategies for preventing teenage pregnancies include sex education starting early in school, availability of contraception for teenagers, family planning counseling, and education to alert parents to the sexuality of their teenagers. Education must be emphasized.
Bad medicine: food intolerance
Authors: Des Spence
Journal: BMJ (2013)

“Do you believe that non-coeliac gluten sensitivity exists?” In a recent poll on bmj.com, 66% of the 941 well educated respondents said that they did—despite the lack of objective scientific evidence.1 2 Many doctors themselves have a gluten-free diet for many reasons, such as heart, bowel, and joint problems; migraine; or just to be generally “healthier.” Modern medicine has a thick veneer of science and evidence, but underneath it is really just opinion⇑. 

Non-coeliac gluten sensitivity is just one of many “food intolerances.” Allergy …
Dynamic effects of acid on Barrett's esophagus. An ex vivo proliferation and differentiation model.
Authors: R C Fitzgerald, M B Omary, G Triadafilopoulos
Journal: Journal of Clinical Investigation (1996)

Barrett's esophagus (BE), or specialized intestinal metaplasia, is a premalignant heterogeneous epithelium associated with reflux and an increased risk for adenocarcinoma. Since acid is a major component of refluxate, we investigated its effects ex vivo on cell differentiation as determined by villin expression; and on cell proliferation, as determined by tritiated thymidine incorporation and proliferating cell nuclear antigen expression. To mimic known physiological conditions, endoscopic biopsies of normal esophagus, BE, and duodenum were exposed, in organ culture, to acidified media (pH 3-5) either continuously, or as a 1-h pulse and compared with exposure to pH 7.4 for up to 24 h. Before culture, villin expression was noted in 25% of BE samples, and increased after 6 or 24 h of continuous acid to 50% or 83% of BE samples, respectively. Increased villin expression correlated with ultrastructural maturation of the brush border. In contrast, an acid-pulse followed by culture at pH 7.4, did not alter villin expression in BE. Moreover, continuous acid exposure blocked cell proliferation in BE, whereas, an acid-pulse enhanced cell proliferation, as compared to pH 7.4. Based on our ex vivo findings, we propose a model in which the diverse patterns of acid exposure in vivo may contribute to the observed heterogeneity and unpredictable progression to neoplasia of BE.
Single-cell phospho-specific flow cytometric analysis demonstrates biochemical and functional heterogeneity in human hematopoietic stem and progenitor compartments
Authors: Kenneth D. Gibbs, Penney M. Gilbert, Karen Sachs, Feifei Zhao, Helen M. Blau, Irving L. Weissman, Garry P. Nolan, Ravindra Majeti
Journal: Blood (2011)
Reviews and Notes: Clinical Pharmacology: Pharmacotherapy: A Pathophysiologic Approach
Authors: Norman Campbell
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 October 1993Reviews and Notes: Clinical Pharmacology: Pharmacotherapy: A Pathophysiologic ApproachNorman Campbell, MDNorman Campbell, MDUniversity of Calgary, Calgary, Alberta, Canada T2N 4N1.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-8-199310150-00033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Pharmacotherapy: A Pathophysiologic ApproachSecond edition. Joseph T. DiPiro, Robert L. Talbert, Peggy E. Hayes, Gary C. Yee, Gary R. Matzke, and L. Michael Posey; eds. 2269 pages. Norwalk, Connecticut: Appleton & Lange; 1993. $110.00.An explosion of information in medicine has occurred in the last few decades, particularly in medical therapeutics. Tremendous advances are evident in the areas of basic and clinical pharmacologic concepts, drug formulations, and therapies. Given this large amount of information, the authors of Pharmacotherapy: A Pathophysiologic Approach have written the text for an audience that includes pharmacy students and practicing pharmacists.The main emphasis in this book is ... Author, Article, and Disclosure InformationAffiliations: University of Calgary, Calgary, Alberta, Canada T2N 4N1. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1993Volume 119, Issue 8Page: 865KeywordsCardiomyopathiesChronic obstructive pulmonary diseaseClinical pharmacologyDrug therapyDrugsForecastingPharmacistsPharmacology ePublished: 15 August 2000 Issue Published: 15 October 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Surface markers for the murine oval cell response
Authors: Craig Dorrell, Laura Erker, Kelsea M. Lanxon‐Cookson, Stephanie L. Abraham, Tristan Victoroff, Simon Ro, Pamela S. Canaday, Philip R. Streeter, Markus Grompe
Journal: Hepatology (2008)

The biology of progenitor activation in the liver is of considerable medical and scientific interest. The powerful genetic tools available for the mouse make it an ideal model system to study this complex process involving many different cell types. However, reagents for the isolation and study of distinct hepatic subpopulations have been quite limited compared to those available for hematopoietic cells. To produce cell surface reactive reagents more specific for the oval cell response, we generated a new collection of monoclonal antibodies by immunization of Fischer rats with enzymatically dispersed nonparenchymal cells from the livers of adult mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Each of the resulting antibodies recognized a surface antigen present on a liver cell subset and permitted the viable isolation of the associated subpopulation by fluorescence-activated cell sorting. Differential activity was observed on normal liver cells and at different stages of oval cell activation, indicating potential utility for progenitor cell identification. The subdivision of liver cells using these tools should facilitate the study of the biology of ductal and periductal hepatic cell types, including progenitors. Conclusion: A new panel of surface reactive monoclonal antibodies to support investigation of the murine oval cell response has been developed. (HEPATOLOGY 2008.)
PHAGOCYTIC IMMUNITY IN STREPTOCOCCUS INFECTIONS
Authors: J. C. Meakins
Journal: The Journal of Experimental Medicine (1909)

1. In infections with streptococcus in man, such as acute septic endocarditis, and tonsillitis, there is produced a powerful opsonic immunity. 2. This opsonic immunity is effective towards the streptococcus which has caused infection but may be ineffective in the presence of streptococcus from other sources. 3. Little benefit can be expected from streptococcus vaccines unless they are prepared from the streptococcus which has caused infection.
Dermatitis Induced by Warfarin
Authors: Pansy Kwong
Journal: JAMA (1978)

THE COUMARIN congeners, especially warfarin sodium, are clinically important for prolonged anticoagulation in patients with various thromboembolic disorders such as pulmonary emboli, deep venous thromboses, and arterial emboli. There is widespread clinical awareness of the hemorrhagic side effects of anticoagulation. However, the literature on the subject of coumarin-induced skin abnormalities is sparse. <h3>Report of a Case</h3> A 52-year-old real estate broker suffered his first episode of thrombophlebitis during World War II. He had several recurrences of his symptoms in the next 30 years, but did not recall having received anticoagulation therapy. On July 22, 1974, he was admitted to the hospital for pain, warmth, and swelling of his left calf. Bilateral lower extremity venograms showed extensive venous thrombi involving virtually the entire deep system and extending up to the level of the knee. The femoral vein was reconstituted, and in the midthigh, there was a persistent filling defect located medially,
Invest in primary care if you want to relieve emergency departments, GP leader says
Authors: G. Iacobucci
Journal: BMJ (2014)

The chairwoman of the Royal College of General Practitioners, Maureen Baker, has criticised the government’s decision to offer financial bailouts to emergency services departments in England and urged ministers to refocus resources on improving services in the community.

Baker said short term and politically motivated interventions like the £500m (€610; $830) fund for emergency services,1 announced last year by the prime minister, David Cameron, would not address the underlying pressures throughout the NHS.

Speaking at the Open Forum conference, “Managing accident and emergency: averting an A&E crisis,” in Manchester on 26 February, Baker urged ministers to look at the …