tbuckley/cabot-search huggingface dataset:
Abstract 1353: Hydrogen sulfide-releasing naproxen inhibits HT-29 human colon cancer cell growth: Modulation of NF-κB
Authors: Diandra E. Nesbitt, Mitali Chattopadhyay, Ravinder Kodela, Daniel Boring, James A. Crowell, Khosrow Kashfi
Journal: Cancer Research (2011)

Abstract Introduction: Chronic inflammation is widely recognized as an underlying etiological factor in carcinogenesis; there is enough evidence to support the use of non-steroidal anti-inflammatory drugs (NSAIDs) as chemopreventive agents. However, their wide use is precluded due to significant toxicity. Recently, a new class of hydrogen sulfide-releasing NSAIDs have been described in which the parent NSAID is covalently linked to a dithiolethione moiety (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) which release hydrogen sulfide. HS-NSAIDs have enhanced safety and efficacy compared to their traditional counterparts. Since NSAIDs are regarded as prototypical chempreventive agents, here we compared naproxen and its hydrogen sulfide-releasing (HS-naproxen) analog using a human colon cancer cell line and also evaluated its effect on NF-κB whose induction is strongly implicated in some cancers. Methods: HS-naproxen was synthesized and purified at our lab with 1H-NMR verification. Cell line: HT-29 human adenocarcimoma; Cell growth: MTT; Cell cycle phase distribution: Flow cytometry; Apoptosis: subdiploid (sub-G0/G1) peak in DNA content histograms; Proliferation: PCNA; NF-κB: enzyme-linked immunosorbent assay (ELISA). GSH levels: colorimetric method. Results: HS-naproxen inhibited the growth of HT-29 cells with an IC50 of 72 ± 5 µM whereas for naproxen the IC50 was 2800 ± 190 µM at 24h. HS-naproxen treatment of HT-29 cells at 0.5xIC50, 1xIC50, and 2xIC50 for 24 hrs induced apoptosis (12 ± 1%, 54 ± 3%, 71 ± 3%), inhibited proliferation (PCNA, 71 ± 3%, 49 ± 5%, 26 ± 4%), and caused a G0/G1 cell cycle block. Activation of NF-κB was inhibited as demonstrated by ELISA, at 0.5xIC50, 1xIC50, and 2xIC50 the reduction was 22 ± 3%, 47 ± 2%, and 62 ± 4% respectively. Cellular GSH levels were also reduced dose-dependently by HS-naproxen, suggesting a condition of oxidative stress. Conclusions: HS-naproxen inhibits HT-29 cell growth and inhibits NF-κB activation. These data suggest that HS-naproxen may be useful as chemopreventive agent against colon cancer and merits further evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1353. doi:10.1158/1538-7445.AM2011-1353
Ultrasound in Diagnosis of Acute Cholecystitis-Reply
Authors: Robert E. Hermann
Journal: JAMA (1976)

In Reply.—  I appreciate the opportunity to learn from Drs Crow and Bartrum about the use and potential value of ultrasound in the diagnosis of acute cholecystitis. I note that the references given along with their letter include a presentation to the Radiologic Society of North America in December 1975 (the month my article was published) and two references not as yet published.  After speaking with our radiologists, I find that we have also installed an ultrasound, Grey-scale unit at the Cleveland Clinic in the past six months, and have begun to assess its use in the diagnosis of cholecystitis. It does show the presence of the gallbladder, the size of the gallbladder, and the presence or absence of stones. It does not provide information on gallbladder function. We are, at present, evaluating its use in patients with acute cholecystitis. I appreciate this information from Drs Crow and Bartrum in
Hepatic Drug Targeting: Phase I Evaluation of Polymer-Bound Doxorubicin
Authors: Leonard W. Seymour, David R. Ferry, David Anderson, Stuart Hesslewood, Peter J. Julyan, Richard Poyner, Jayne Doran, Annie M. Young, Sally Burtles, David J. Kerr
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2. PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine. Targeting, toxicity, and efficacy were evaluated in 31 patients with primary (n = 25) or metastatic (n = 6) liver cancer. Body distribution of the radiolabelled polymer conjugate was assessed using gamma-camera imaging and single-photon emission computed tomography. RESULTS: The polymer was administered by intravenous (IV) infusion over 1 hour, repeated every 3 weeks. Dose escalation proceeded from 20 to 160 mg/m2 (doxorubicin equivalents), the maximum-tolerated dose, which was associated with severe fatigue, grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after administration, 16.9% ± 3.9% of the administered dose of doxorubicin targeted to the liver and 3.3% ± 5.6% of dose was delivered to tumor. Doxorubicin-polymer conjugate without galactosamine showed no targeting. Three hepatoma patients showed partial responses, with one in continuing partial remission 47 months after therapy. CONCLUSION: The recommended PK2 dose is 120 mg/m2, administered every 3 weeks by IV infusion. Liver-specific doxorubicin delivery is achievable using galactosamine-modified polymers, and targeting is also seen in primary hepatocellular tumors.
A fairer world: recognising women's choices
Authors: A. Jain
Journal: BMJ (2014)

Has human civilisation progressed since the 18th century? Instances of violation of women’s rights across the world don’t seem to suggest so.

The Delhi gang rape in 2012 sparked intense public outrage. It propelled the Indian bureaucracy to reflect on and seek to mend existing systems that a survivor encounters in the quest for recovery, rehabilitation, and justice. A positive outcome has been recognition of the health needs of the survivor, and the introduction of standard guidelines for medical examination and treatment. The new guidelines forbid the two finger test, an archaic examination wherein doctors report on laxity of the vaginal introitus to imply habitual sexual intercourse. Not only is this unscientific, it is clearly irrelevant to the assault, and is violating …
Pathological Laughing
Authors: David Morland, Valérie Wolff, Cyrille Blondet, Christian Marescaux, Izzie Jacques Namer
Journal: Clinical Nuclear Medicine (2015)

We present the case of a 40-year-old man consulting for uncontrollable episodes of laughing related to emotional lability and not systematically linked to feelings of happiness. Seven months earlier he had presented a pontine ischemic stroke related to an occlusion of the basilar and left vertebral arteries. No epileptic activity or new MRI brain lesions were found. Brain perfusion SPECT performed showed marked hypoperfusion in the right frontal inferior and temporoinsular regions, suggesting a diaschisis phenomenon caused by pontine lesions and highlighted laughing regulation pathways. The patient was successfully treated with a serotonergic reuptake inhibitor, fluoxetine.
Dung Lung: A Report of Toxic Exposure to Liquid Manure
Authors: LIDA N. OSBERN
Journal: Annals of Internal Medicine (1981)

The use of liquid manure storage facilities poses several serious threats: toxic gas inhalation, asphyxiation, aspiration of liquid manure, and infection. Hydrogen sulfide poisoning in a manure storage pit resulted in three deaths. Two of the persons who died had massive aspiration of liquid manure; the third had severe pulmonary edema but had not aspirated manure. The clinical course of the patient who survived was complicated by hemodynamic instability, adult respiratory distress syndrome, and infection. These accidents can be prevented by the use of a self-contained breathing apparatus and a safety line, as well as the presence of a second person for rescue if necessary. Recommendations for treatment are mainly supportive, including cardiopulmonary resuscitation, mechanical ventilation, oxygen, and positive end-expiratory pressure. Nitrites may speed recovery but in excess can cause other complications.
Serial PET Scans Demonstrate the Success and Limitations of Antiangiogenic Treatment in a Case of Lung Adenocarcinoma
Authors: Zhaohui Zhu, Fang Li
Journal: Clinical Nuclear Medicine (2008)

Antiangiogenic treatment is a new method for molecular-targeted therapy for solid tumors. In a 54-year-old man with stage IV lung adenocarcinoma, the success and limitations of antiangiogenic treatment were visually demonstrated by serial F-18 FDG PET scans on a Siemens ECAT EXACT HR+ system. On one hand, the combination of 2 antiangiogenic agents, bevacizumab and erlotinib, successfully inhibited the adenocarcinoma of the lung with probable resistance to first-line chemotherapy and stably controlled the disease as progression-free for more than 1 year. On the other hand, the additionally used bevacizumab during the first-line chemotherapy and the erlotinib used alone later were insufficient to control the malignancy. In addition, the successful antiangiogenic treatment inhibited the mass forming of the malignancy but did not extinguish the malignant cells. A small amount of cancer cells remained in the resected residual primary tumor without prominent F-18 FDG accumulations; the carcinoembryonic antigen (CEA) levels stayed higher than normal, although relatively stable during the treatment, and the disease relapsed rapidly when one of the antiangiogenic agents, bevacizumab, was stopped. Therefore, the antiangiogenic treatment should be done continuously with effective dosages. This case also indicated that serial PET follow-up might be one of the best ways to evaluate newly developed antitumor agents.
Implications of the Women's Liberation Movement for Psychotherapy
Authors: JOY K. RICE, DAVID G. RICE
Journal: American Journal of Psychiatry (1973)

The authors examine the implications of the women's liberation movement for current psychotherapeutic theory and practice in terms of the antifeminine Freudian position, the predominance of male therapists, the concept of role unhappiness as psychopathological, and the threat to the therapist's social power. Consideration of role conflict in sociological terms instead of the intrapsychic rubric is especially emphasized. The authors also discuss related issues concerning the training of therapists and propose a model using male and female cotherapists.
Response to Letter Regarding Article, “Relationship of Echocardiographic Dyssynchrony to Long-Term Survival After Cardiac Resynchronization Therapy”
Authors: John Gorcsan, Olusegun Oyenuga, Phillip J. Habib, Hidekazu Tanaka, Evan C. Adelstein, Hideyuki Hara, Dennis M. McNamara, Samir Saba
Journal: Circulation (2011)
Lack of Effect of Aspirin in Asymptomatic Patients with Carotid Bruits and Substantial Carotid Narrowing
Authors: Robert Cote
Journal: Annals of Internal Medicine (1995)

Objective: To determine the effectiveness of aspirin in preventing ischemic events in patients with asymptomatic carotid stenosis. Design: Double-blind, placebo-controlled trial. Setting: University-affiliated hospitals. Patients: 372 neurologically asymptomatic patients with carotid stenosis of 50% or more in at least one artery as determined by luminal diameter reduction on duplex ultrasonography. Intervention: Patients were randomly assigned to receive either enteric coated aspirin, 325 mg/d, or identically appearing placebo. Duration of therapy was 2.0 years for the aspirin recipients and 1.9 years for the placebo recipients. Outcome Measures: Patients were scheduled for a clinical examination every 6 months for assessment of the occurrence of any clinical event in the composite end point, which consisted of transient ischemic attack, stroke, myocardial infarction, unstable angina, or death. Results: At baseline, the 188 patients receiving aspirin and the 184 patients receiving placebo had similar demographic, ultrasonographic, and laboratory characteristics. The median duration of follow-up was 2.3 years. The annual rate of all ischemic events and death from any cause was 12.3% for the placebo group and 11.0% for the aspirin group (P = 0.61). The Cox proportional-hazards analysis yielded an adjusted hazard ratio (aspirin-placebo) of 0.99 (95% CI, 0.67 to 1.46; P = 0.95). The annual rates for vascular events only were 11% for the placebo group and 10.7% for the aspirin group (P = 0.99). The multivariate analysis yielded a hazard ratio of 1.08 (CI, 0.72 to 1.62; P = 0.71). Conclusion: Aspirin did not have a significant long-term protective effect in asymptomatic patients with high-grade (≥ 50%) carotid stenosis. *For members of the Asymptomatic Cervical Bruit Study Group and participating institutions, see the Appendix.
Physical Medicine and Orthopaedics
Authors: B. Kiernander
Journal: BMJ (1941)

<h3>Background</h3> Despite having high comorbidity rates and shortened life expectancy, patients with ESKD may harbor unrealistically optimistic expectations about their prognoses. Whether this affects resuscitation orders is unknown. <h3>Methods</h3> To determine whether do-not-resuscitate (DNR) orders differ among patients with ESKD compared with other critically ill patients, including those with diseases of other major organs, we investigated DNR orders on admission to intensive care units (ICUs) among 106,873 patients in the United States. <h3>Results</h3> Major organ disease uniformly associated with increased risk of hospital mortality, particularly for cirrhosis (adjusted odds ratio [aOR], 2.67; 95% confidence interval [95% CI], 2.30 to 3.08), and ESKD (aOR, 1.47; 95% CI, 1.31 to 1.65). Compared with critically ill patients without major organ disease, patients with stroke, cancer, heart failure, dementia, chronic obstructive pulmonary disease, and cirrhosis were statistically more likely to have a DNR order on ICU admission; those with ESKD were not. Findings were similar when comparing patients with a single organ disease with those without organ disease. The disconnect between prognosis and DNR use was most notable among Black patients, for whom ESKD (compared with no major organ disease) was associated with a 62% (aOR, 1.62; 95% CI, 1.27 to 2.04) higher odds of hospital mortality, but no appreciable difference in DNR utilization (aOR, 1.06; 95% CI, 0.66 to 1.62). <h3>Conclusions</h3> Unlike patients with diseases of other major organs, critically ill patients with ESKD were not more likely to have a DNR order than patients without ESKD. Whether this reflects a greater lack of advance care planning in the nephrology community, as well as a missed opportunity to minimize potentially needless patient suffering, requires further study.
Relation of Adrenal Androgen to Insulin Levels
Authors: John E. Nestler
Journal: Annals of Internal Medicine (1993)

Letters15 May 1993Relation of Adrenal Androgen to Insulin LevelsJohn E. Nestler, MDJohn E. Nestler, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-10-199305150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The report by Barrett-Connor [1] that serum levels of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate are decreased in untreated men with mild type II diabetes mellitus is thought provoking. During the past decade, it has become apparent that insulin may act as a physiologic regulator of human steroid hormone biosynthesis [2]. Although serum insulin levels were not reported in Barrett-Connor's study [1], it seems likely that the untreated men with type II diabetes mellitus were insulin resistant and hyperinsulinemic.Insulin has been shown to lower acutely serum DHEA and DHEA-sulfate levels in men and women [2]. ...References1. Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non–insulin-dependent diabetes mellitus. Ann Intern Med. 1992; 117:807-11. Google Scholar2. Nestler JE, Strauss JF III. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinol Metab Clin North Am. 1991; 20:807-23. Google Scholar3. Beer NA, Jakubowicz DJ, Beer RM, Arocha IR, Nestler JE. Effects of nitrendipine on glucose tolerance and serum insulin and dehydroepiandrosterone-sulfate levels in insulin-resistant obese and hypertensive men. J Clin Endocrinol Metab. 1993; 76:178-83. Google Scholar4. Barrett-Connor E, Khaw KT, Yen SS. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986; 315:1519-24. Google Scholar5. Nestler JE, Clore JN, Blackard WG. Dehydroepiandrosterone: the missing link between hyperinsulinemia and atherosclerosis? FASEB J. 1992; 6:3073-5. Google Scholar Author, Article, and Disclosure InformationAuthors: John E. Nestler, MDAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome 15 May 1993Volume 118, Issue 10Page: 826KeywordsAndrogensDiabetes mellitusGlucose toleranceHyperinsulinemiaHypoglycemicsInsulinInsulin resistanceObesityOverweightSteroid hormones ePublished: 15 August 2000 Issue Published: 15 May 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A concern that drug companies cannot ignore
Authors: E. Wager
Journal: Journal of the Royal Society of Medicine (2005)

A report by the House of Commons Health Committee into the influence of the UK pharmaceutical industry has recommended that companies should publish the results of all their trials and follow guidelines for responsible publication practice. 1Cynics may argue that such reports rarely have much influence over powerful commercial companies and that governments usually ignore their recommendations unless they support existing policies.But this call for greater transparency and responsibility echoes similar calls which, taken together, form a crescendo that is hard to ignore.Earlier events that may have focused the minds of drug companies and made them more receptive to the latest recommendations include the fine of $240 million plus $152 million damages awarded against Pfizer/Warner-
Long-term Anticoagulant Therapy: Complications and Control.
Authors: D. H. Mosley
Journal: Annals of Internal Medicine (1963)

s1 April 1963Long-term Anticoagulant Therapy: Complications and Control.D. H. Mosley, M.D., I. J. Schatz, M.D., G. M. Breneman, M.D., F.A.C.P., J. W. Keyes, M.D., F.A.C.P.D. H. Mosley, M.D.Search for more papers by this author, I. J. Schatz, M.D.Search for more papers by this author, G. M. Breneman, M.D., F.A.C.P.Search for more papers by this author, J. W. Keyes, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-714_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAs experience in the use of anticoagulant drugs accumulates, analysis of the incidence of complications is necessary to assess the risk of out-patient therapy.All patients treated with long-term anticoagulants and out-patients during the period from August, 1961, to August, 1962, were reviewed. The incidence of complications and the adequacy of control was studied for this 1-year period, though the great majority (86%) had received treatment for over 1 year. All patients were treated for at least 3 months.Of the 978 patients studied, 39 (4%) no longer received therapy during this period; 15 patients received no treatment because of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: D. H. Mosley, M.D.; I. J. Schatz, M.D.; G. M. Breneman, M.D., F.A.C.P.; J. W. Keyes, M.D., F.A.C.P.Affiliations: Detroit, Mich. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 714-715KeywordsAnticoagulant therapyAnticoagulantsOutpatientsPatients ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization
Authors: Steven Goossens, Viktor Janzen, Sonia Bartunkova, Tomomasa Yokomizo, Benjamin Drogat, Mihaela Crisan, Katharina Haigh, Eve Seuntjens, Lieve Umans, Tamara Riedt, Pieter Bogaert, Lieven Haenebalcke, Geert Berx, Elaine Dzierzak, Danny Huylebroeck, Jody J. Haigh
Journal: Blood (2011)
Pax6 Exerts Regional Control of Cortical Progenitor Proliferation via Direct Repression of Cdk6 and Hypophosphorylation of pRb
Authors: Da Mi, Catherine B. Carr, Petrina A. Georgala, Yu-Ting Huang, Martine N. Manuel, Emily Jeanes, Emi Niisato, Stephen N. Sansom, Frederick J. Livesey, Thomas Theil, Kerstin Hasenpusch-Theil, T. Ian Simpson, John O. Mason, David J. Price
Journal: Neuron (2013)

The mechanisms by which early spatiotemporal expression patterns of transcription factors such as Pax6 regulate cortical progenitors in a region-specific manner are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6+/+ and Pax6−/− cortices and identified many negatively regulated cell-cycle genes, including Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes that directly promote the mechanics of the cell cycle, and we found that Pax6 inhibits pRb phosphorylation and represses genes involved in DNA replication. Our results indicate that Pax6's modulation of cortical progenitor cell cycles is regional and direct.
705-6 Post-Infarct Ventricular Tachycardia: Success Rate of Catheter Ablation
Authors: Steven A. Rothman, Henry H. Hsia, Sergio F. Cossú, Lisa M. Thome, Nancy M. Adelizzi, Deborah M. Whitley, Alfred E. Buxton, John M. Miller.
Journal: Journal of the American College of Cardiology (1995)
The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation
Authors: Andrea C. Carpenter, John R. Grainger, Yumei Xiong, Yuka Kanno, H. Hamlet Chu, Lie Wang, Shruti Naik, Liliane dos Santos, Lai Wei, Marc K. Jenkins, John J. O’Shea, Yasmine Belkaid, Rémy Bosselut
Journal: Immunity (2012)
Mortality in patients with bleeding peptic ulcer when those aged 60 or over are operated on early.
Authors: K E Wheatley, J H Snyman, S Brearley, M R Keighley, P W Dykes
Journal: BMJ (1990)

women with detrusor instability and those with genuine stress incontinence, suggests that future research into aetiological factors of detrusor instability should con- centrate on physical, and particularly neurological, aspects.
811-2 Multisite pacing improves synchronization of regional ventricular contraction as assessed by three-dimensional echocardiography in patients with single ventricle congenital heart disease
Authors: Frank Zimmerman, Lynn Weinert, Victor Mor-Avi, Emile Bacha, Joanne Starr, Lissa Sugeng, Roberto Lang
Journal: Journal of the American College of Cardiology (2004)
Diabetes Mellitus as a Predictor for Radial Artery Vasoreactivity in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Bikram P. Choudhary, Charalambos Antoniades, Alison F. Brading, Antony Galione, Keith Channon, David P. Taggart
Journal: Journal of the American College of Cardiology (2007)