tbuckley/cabot-search huggingface dataset:
Abstract 1643: Withaferin A analogues up-regulate the MAPK and glutathione metabolic pathways prior to activation of apoptosis in pancreatic cancer cells
Authors: Daruka Mahadevan, Xiaobing Liu, Wenqing Qi, Laurence Cooke, Kithsiri Wijevatne, Marilyn Marron, Leslie Gunatilaka
Journal: Cancer Research (2010)

Abstract Withaferin A is a natural product known to possess anti-cancer activity. Here we studied the effect of Withaferin A and 11 of its analogs on differentiation state-specific pancreatic cancer cell lines. Three pancreatic cell lines Panc-1 (poorly-differentiated), MiaPaca-2 (moderately differentiated) and BxPC-3 (well differentiated) were treated with 11 analogs and cell proliferation was examined by MTS assays. The IC50 of these 11 analogs were &amp;lt;4.0 µM suggesting they have growth inhibitory effects on pancreatic cancer cell proliferation. Two of these 11 analogs, named KW-120-94-1 and KW-120-95-1 were selected for further study. The IC50s of KW-120-94-1 and KW-120-95-1 were 2.25, 0.56 µM (Panc-1); 1.53, 0.52 µM (MiaPaca-2) and 0.45, 0.29 µM (BxPC-3) respectively. Apoptosis was analyzed by morphology (Acridine Orange and Ethidium Bromide staining), flow cytometry (Annexin V-FITC and Propidium Iodide staining) and PARP cleavage. The data showed that apoptosis was induced both in BXPC-3 and MiaPaca-2 cells in a dose-dependent manner. However, Panc-1 cells were in general resistant to apoptosis. In BxPC-3 cells apoptosis was induced as early as 6 hours after KW-120-95-1 treatment at 1.5µM. To determine the Withaferin A analog dependent ‘tumor profile signature’, gene expression profiling by Affymetrix microarrays were performed in the 3 pancreas cancer cell lines. The cells were treated with KW-120-95-1 for 8 hr at 1.5µM. Differential gene expression was analyzed by ANOVA which identified 33 (MiaPaca-2), 54 (Panc-1) and 48 (BXPC-3) gene changes. The Fisher exact test demonstrated that MAPK signaling and glutathione metabolism pathways were over-expressed within the genes that changed with treatment. Western blotting and real-time RT-PCR were utilized to confirm gene expression changes identified in the MAPK pathway (HSPA1A/HSPA1B, c-Jun) and glutathione metabolism pathway (GCLC, GPX2 and GPX3). Taken together, our data indicate that Withaferin A analogs inhibit pancreatic cancer proliferation and induces apoptosis by activating the MAPK and glutathione (stress) pathways. The molecular target(s) of Withaferin A and analogs are likely to function by activating the MAPK signaling and glutathione metabolism pathways. 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 1643.
Clindamycin-Associated Colitis
Authors: KIRON M. DAS
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 March 1975Clindamycin-Associated ColitisKIRON M. DAS, M.D., PH.D., WILLIAM F. ERBER, M.D.KIRON M. DAS, M.D., PH.D.Search for more papers by this author, WILLIAM F. ERBER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-3-426_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the article on clindamycin-associated colitis by Tedesco, Barton, and Alpers (1) and the editorial (2) published in the October issue of the Annals. We wish to report a case of clindamycin-associated colitis, in which we studied the electron microscopic and immunohistochemical features of the colonic mucosa in addition to other routine examinations.This 79-year-old white man developed the syndrome with profuse watery diarrhea without blood after a 2-week course of clindamycin therapy. Barium enema showed the features consistent with ulcerative colitis. Colonoscopy showed classical yellowish white plaques (1 to 6 mm in diameter)...References1. TEDESCOBARTONALPERS FRD: Clindamycin-associated colitis. Ann Intern Med 81:429-433, 1974 LinkGoogle Scholar2. WELLS R: Clindamycin-associated colitis. Ann Intern Med 8:547-548, 1974 LinkGoogle Scholar3. BRANDTZAEGBAKLIENFAUSA PKO: Immunochemical characterization of local immunoglobulin formation in ulcerative colitis. Gastroenterology 66:1123-1136, 1974 CrossrefMedlineGoogle Scholar4. MCGOVERNGOULSTOM VS: lschaemic enterocolitis. Gut 6:213-220, 1965 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Gastroenterology-Liver Disease Albert Einstein College of Medicine Bronx, New York 10461 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byLEATHER DYES 1 March 1975Volume 82, Issue 3Page: 426-427KeywordsBloodClindamycinColitisColonoscopyDiarrheaElectron microscopyMucous membranesUlcerative colitis Issue Published: 1 March 1975 PDF downloadLoading ...
Skin Tags: A Cutaneous Marker for Colonic Polyps
Authors: JAMES LEAVITT
Journal: Annals of Internal Medicine (1983)

The relation between adenomatous colonic polyps and the development of adenocarcinoma of the colon is well established. An association between skin tags and colonic polyps in patients with acromegaly has also been reported. To ascertain if skin tags are a cutaneous marker for colonic polyps independent of the presence of acromegaly, 100 men referred for colonscopy were studied. Forty-six patients had colonic polyps and 37 also had skin tags; the correlation was highly significant (p < 0.005). The sensitivity and specificity of the presence of skin tags serving as a cutaneous marker for adenomatous colonic polyps were both greater than 75%. Thus, at least in this population, skin tags may serve as a means for identifying patients at increased risk for having colonic polyps.
THE COMING REVISION OF THE PHARMACOPEIA OF THE UNITED STATES.
Authors: M. I. WILBERT
Journal: JAMA (1906)

While therapeutic measures, other than drugs and medicines, are very properly receiving an ever increasing amount of attention we must not lose sight of the fact that drug therapy can not, as yet, be considered among the practices that we can well do without. From evident indications it is probable that drugs and medicines will continue to occupy a very important position in the prevention as well as in the treatment of disease for decades, if not for centuries to come. If the continued need for drugs and medicinal preparations be admitted to be evident it will readily be acknowledged that the need for a more systematic and detailed knowledge of the nature, uses and limitations of the several substances that are used in drug therapy can not be questioned and will, therefore, serve as an apology for introducing what may appear to some to be a hackneyed and uninteresting
Management of Aortoiliac Reconstruction Complicated by Sepsis and Hemorrhage
Authors: Frank J. Veith, James M. Hartsuck, Chilton Crane
Journal: New England Journal of Medicine (1964)

SEPSIS involving a vascular prosthesis, fortunately rare, is a most serious complication of arterial surgery. Although there are clinical and experimental examples of periprosthetic sepsis that have responded favorably to drainage, debridement, irrigation and systemic antibiotics1 2 3 4 5 6 7 the usual outcome of such sepsis is either thrombosis of the graft or, more commonly, bleeding from one of the vascular suture lines. When a suture line is involved in the septic process leakage, resulting in free bleeding or a false aneurysm, is inevitable. Once such leakage has occurred, several authors have shown the futility of any procedure that does not include interruption of . . .
Faecal peritonitis after laxative preparation for barium enema
Authors: D Cave-Bigley
Journal: BMJ (1982)

better staffed welfare homes with trained nursing staff, physiotherapists, occupational therapists, speech therapists, social workers, and chiropodists, and with a regular visit from the GP, seem to be the answer.Further- more, the criteria for acceptability of patients for these welfare homes will need to be redefined.Certainly a significant number of chronic elderly invalids do not need to be greeted by a consultant geriatrician on the ward round, and in any case a hospital can never be a home; but the welfare home would be a home for its residents.
India must act to stem rise of unnecessary medical interventions, says World Bank
Authors: C. Travasso
Journal: BMJ (2014)

The overuse of medical tests and interventions is emerging as a serious problem in India, and the country needs to take action to stop it worsening, the World Bank has warned.1

People in India with private voluntary health insurance are two to three times more likely to be hospitalised than the national average, said an article by the anti-poverty agency. “Many of these interventions deliver only marginal benefits and can actually harm the patients, leading to unnecessary suffering, especially among the frail and elderly,” it noted. 

The article reported a recent conference held by the World Bank on finding ways to ensure the medical necessity of care, attended by healthcare …
Anticoagulants cause the most serious adverse events, finds US analysis
Authors: J. Lenzer
Journal: BMJ (2012)

A report by a watchdog group has concluded that prescribed medicines are “one of the most significant perils to human health resulting from human activity.” The group based their conclusion on their analysis of the US Food and Drug Administration’s database of serious adverse events.

The report was published on 31 May in QuarterWatch, a publication of the Institute for Safe Medication Practices, a non-profit organisation dedicated to “medication error prevention and safe medication use” based in Horsham, Pennsylvania.1 It calculated that in 2011 prescription drugs were associated with two to four million people in the US experiencing “serious, disabling, or fatal injuries,” including 128 000 deaths.

According to the US Centers for Disease Control and Prevention, 48% of the …
African leaders join forces to boost fight against malaria
Authors: P. Moszynski
Journal: BMJ (2009)

A group of African leaders has launched a new initiative to defeat malaria, which, it says, “represents one of the biggest health and economic challenges to the continent.”

The African Leaders’ Malaria Alliance (www.alma2015.org) was inaugurated on 23 September at the United Nations General Assembly in New York. It brings together 20 of the continent’s heads of state and governments to launch a “coordinated and effective response to malaria.”

The alliance intends to provide “a high level forum to ensure efficient procurement, distribution, and utilisation of malaria control interventions.” It also aims to “facilitate the sharing of effective malaria control practices and ensure that malaria remains high on the global policy agenda.”

As a major killer …
Working against the Grain
Authors: David P. Steensma
Journal: Annals of Internal Medicine (2006)

On Being a Doctor2 May 2006Working against the GrainDavid P. Steensma, MDDavid P. Steensma, MDFrom the Mayo Clinic, Rochester, MN 55905.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-9-200605020-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I paused under the carved lintel that crowned the doorway of his battered clapboard farmhouse. Despite the sanction of the Hippocratic oath (Into whatever houses I enter, I will go into them for the benefit of the sick …), I remain uncomfortable when entering my patients' homes, especially when there is little to offer beyond the dubious benefit of my presence. The probing intimacies of routine medical practice don't bother me much anymore, but home visits still seem a deeper invasion of privacy—like sitting abruptly on the corner of an occupied hospital bed, or eavesdropping on an unguarded telephone conversation ... Author, Article, and Disclosure InformationAffiliations: From the Mayo Clinic, Rochester, MN 55905.Corresponding Author: David P. Steensma, MD, Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905; e-mail, Steensma.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 May 2006Volume 144, Issue 9Page: 697-698KeywordsBloodHematology and oncologyMelanomaNeurosurgerySurgeonsSweatTasteTeaTouchVaccines ePublished: 2 May 2006 Issue Published: 2 May 2006 CopyrightCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.
Authors: A Vitiello, G Ishioka, H M Grey, R Rose, P Farness, R LaFond, L Yuan, F V Chisari, J Furze, R Bartholomeuz
Journal: Journal of Clinical Investigation (1995)

Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target.Because most CTL peptide epitopes are poor immunogens, we specifically modified them by cova- lently attaching two additional components: a T helper pep- tide epitope and two lipid molecules.Using the murine in- fluenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that per- sisted for > 1 yr.Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects.The three vaccine components included HBV core antigen pep- tide 18-27 as the CTL epitope, tetanus toxoid peptide 830- 843 as the T helper peptide, and two palmitic acid molecules as the lipids.A dose escalation trial (5, 50, and 500 jIg) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response.A dose-response curve was observed and five out of five subjects responded to the 500-jig dose.(
Radiological Studies of Pituitary Tumors
Authors: Martin L. Lazar
Journal: JAMA (1979)

<h3>To the Editor.—</h3> There is an increasingly widespread awareness of and interest in the manifestations of the medical<sup>1</sup>(241:573, 1979) and surgical management of pituitary tumors. The recent medical reports published inThe Journaland elsewhere by staff writer Elizabeth Rasche González<sup>2</sup>(242:401, 1979) are to be congratulated. Her reporting was comprehensive and well presented. There is one particular point to which she referred that may be of interest to readers and of importance to their patients. It is regarding the roentgenographic evaluation of patients suspected to have a pituitary tumor. Routine skull roentgenograms with cone views of the sella turcica are generally recommended as the initial film studies. Polytomographic views of the sella are also considered useful in both the evaluation of microadenomas and macroadenomas. Neither of these studies carries major risk to the patient. However, pneumoencephalography has been widely used and recommended for the evaluation of
Comparison of Countershock with Direct and Alternating Current in External Cardiac Defibrillation
Authors: Robert M. Stanzler, Richard L. Tannen, Sidney Alexander, Arthur A. Sasahara
Journal: New England Journal of Medicine (1963)

THE combined use of external cardiac massage and external electric defibrillation, as developed by Kouwenhoven et al.1 and Zoll and his associates,2 has added new dimensions to the resuscitation of the fibrillating ventricle. Alternating-current countershock has proved its value in this and in the elective termination of less catastrophic arrhythmias.3 , 4 Recently, Lown and his co-workers5 showed that in dogs a direct-current discharge from a storage capacitor was safer and more effective than alternating-current countershock. To our knowledge this fact has not been substantiated in human beings. A direct comparison of the two methods in the termination of ventricular tachycardia and . . .
Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection
Authors: Richard K. Sterling, Melissa J. Contos, Paula G. Smith, R. Todd Stravitz, Velimir A. Luketic, Michael Fuchs, Mitchell L. Shiffman, Arun J. Sanyal
Journal: Hepatology (2008)

Hepatic steatosis has been reported in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. However, the features of steatohepatitis, including cytologic ballooning and pericellular fibrosis, its risk factors, and the impact on disease severity in such patients are unknown. To assess this, we prospectively reviewed liver histology in consecutive coinfected patients to define the prevalence and severity of the features of steatohepatitis, its risk factors, and its impact on the severity of liver disease. A total of 222 subjects (74% male, mean age 45, 78% African American, 90% genotype 1) were studied. The mean body mass index (BMI) was 26, and 18% had a BMI >30. The prevalence of risk factors for steatosis were: diabetes (31%), hypertension (15%), dyslipidemia (8%), metabolic syndrome (9%), and alcohol abuse (21%). Steatosis was present in 23% and steatohepatitis was present in 17%. The steatosis was mild (5%-33%) in 19%, and moderate to severe (>33%) in 4%. Cytologic ballooning and pericellular fibrosis were present in 30% and 13%, respectively. The mean Ishak score was 6.9, and 33% had bridging fibrosis or cirrhosis. Both steatosis and cytologic ballooning were associated with BMI, metabolic syndrome, and insulin resistance, and presence of either was strongly associated with advanced fibrosis (P < 0.0001). By multiple logistic regressions, the following associations were identified: increased BMI, diabetes, and genotype 3 with steatosis; diabetes with cytologic ballooning; and longer duration of infection with steatohepatitis. Conclusion: Steatosis and steatohepatitis are present in 23% and 30%, respectively, of patients with HIV/HCV coinfection, and both are associated with an increased risk of having advanced fibrosis. Although we did identify genotype 3, increased BMI, and diabetes as risk factors, we found no independent association with antiretroviral therapy. (HEPATOLOGY 2008;47:1118–1127.)
Treatment of Mental Disorders
Authors: John P. Callan
Journal: JAMA (1983)

This soft-cover multiauthored book presents the state of the science and also the art of psychiatric treatments. It is a comprehensive treatise that documents the extensive progress of recent years in the field of psychiatric treatment. In many respects, this volume is a complimentary book to the<i>Diagnostic and Statistical Manual of Mental Disorders</i>, edition 3 (<i>DSM</i>3) (American Psychiatric Association, 1980).<i>DSM</i>3 describes salient clinical findings in a systematic manner for each psychiatric illness without reference to treatment. This book includes the clinical findings in psychiatric illness, and it approaches the treatment of such illness in a standard systematized manner that is similar to<i>DSM</i>3. The publication provides mental health practitioners with a wide range of treatments for any given condition, and it does not adhere to an exclusive school of therapy. Rather, it integrates physical, biologic, chemical, neurophysiological, and psychological (behavioral, group, family, and individual) modes
Molecular monitoring and stepwise preemptive therapy for Epstein–Barr virus viremia after allogeneic stem cell transplantation
Authors: Qifa Liu, Li Xuan, Hui Liu, Fen Huang, Hongsheng Zhou, Zhiping Fan, Ke Zhao, Meiqing Wu, Lanping Xu, Xiao Zhai, Fuhua Zhang, Can Liu, Jing Sun, Xiaojun Huang
Journal: American Journal of Hematology (2013)

The optimal preemptive therapy for Epstein–Barr virus (EBV)‐associated diseases remains under discussion. We developed a stepwise preemptive therapy (antiviral agents and reduction of immunosuppressants [RI] followed by rituximab) for EBV viremia, based on duration of EBV viremia and changes of viral loads. The blood EBV‐DNA loads were regularly monitored by quantitative real‐time polymerase chain reaction in 251 recipients undergoing allogeneic stem cell transplantation. The 3‐year cumulative incidence of EBV viremia and EBV‐associated diseases were 31.1% ± 3.1% and 15.6% ± 2.5%, which rose steeply with greater numbers of major risk factors. Of the 64 patients undergoing first‐step preemption, 24 achieved complete response (CR) and 40 showed no response, including 25 progressing to EBV‐associated diseases. The effective rates of antiviral agents and RI plus antiviral agents were 2/16 and 22/48 ( P = 0.017). Fourteen achieved CR and one progressed to lymphoproliferative disease in the 15 patients undergoing rituximab preemption. Of the 26 patients progressing to EBV‐associated diseases during preemptive therapy, 20 obtained CR in the 23 cases with rituximab‐based treatments. The preemptive efficacy of RI plus antiviral agents was correlated with the numbers of major risk factors ( r s = −0.298; P = 0.04). B‐cell reconstitution was significantly delayed for at least 6 months in patients with rituximab preemption. The risk of herpesvirus infection was similar in patients who showed effective progress to first‐step and rituximab preemption ( P = 0.094). RI plus antiviral agents could be given priority to low‐risk patients, whereas more frequent monitoring of blood EBV‐DNA and earlier preemptive rituximab should be advocated in high‐risk patients. Am. J. Hematol. 88:550–555, 2013. © 2013 Wiley Periodicals, Inc.
The management of H pylori infection
Authors: E A J Rauws, R W M v. d. Hulst
Journal: BMJ (1998)

Helicobacter pylori is the single most important pathogen in peptic ulcer disease since its eradication leads to cure.1 As a result, a National Institutes of Health consensus meeting in 1994 recommended giving anti- H pylori treatment to all patients with active peptic ulcer disease or a history of it and proved infection.2 In 1996 the consensus meeting of the European Helicobacter Study Group in 1996 made similar recommendations and added bleeding peptic ulcers and low grade MALT lymphoma to the list.3 Eradication for other indications remains more controversial. What therefore is the current best evidence on managing H pylori infection, and which is the best treatment?

Though the need for eradication in peptic ulcer disease is agreed, there is also evidence for eradicating H pylori in patients with advanced and progressively worsening forms of gastritis such as intestinal metaplasia, glandular atrophy, and erosive or hypertrophic forms of gastritis, and after resection for early gastric cancer.3 A recent prospective study, however, showed that the degree of intestinal metaplasia and atrophy remained unchanged despite successful eradication.4 This finding should temper the belief that …
GMC faces challenge over withdrawing treatment
Authors: C. Dyer
Journal: BMJ (2004)

The General Medical Council faces an unprecedented challenge in the High Court in London next month to its guidelines for doctors on withholding and withdrawing life prolonging treatment.

A man with cerebellar ataxia claims that the guidance, published in 2002 after extensive consultation, is unlawful and effectively allows doctors to perform euthanasia.

Leslie Burke, 43, from Lancaster, is capable of making his own decisions, but he fears that doctors may decide at a point when he is no longer competent that his life is not worth living and discontinue artificial feeding.

The GMC's guidelines cover the circumstances in which doctors may withhold or withdraw artificial nutrition and …