tbuckley/cabot-search huggingface dataset:
Pregnancy-Related Thromboembolism
Authors: Arumugam Manoharan
Journal: Annals of Internal Medicine (1997)

Letters15 July 1997Pregnancy-Related ThromboembolismArumugam Manoharan, MDArumugam Manoharan, MDSt. George Hospital; Kogarah, Sydney, AustraliaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-2-199707150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the informative article by Friederich and colleagues [1] and the editorial by Lee [2] on thromboembolic disease and pregnancy. Low-molecular-weight heparin, recommended by Friederich and colleagues and Lee, has been effectively and safely used for thromboprophylaxis during pregnancy [3, 4]. However, no information seems to be available about the drug's safety in relation to breast feeding, and drug companies advise against its use during the puerperium in breast-feeding patients. I would appreciate the authors' comments on this issue.References1. Friederich PW, Sanson BJ, Simioni P, Zanardi S, Huisman MV, Kindt I, et al. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med. 1996; 125:955-60. Google Scholar2. Lee RV. Thromboembolic disease and pregnancy: are all women equal? [Editorial] Ann Intern Med. 1996; 125:1001-3. Google Scholar3. Manoharan A. Use of low-molecular weight heparin during pregnancy [Letter]. J Clin Pathol. 1994; 47:94-5. Google Scholar4. Sturridge F, de Swiet M. The use of low-molecular weight heparin for thromboprophylaxis in pregnancy. Br J Obstet Gynaecol. 1994; 101:69-71. Google Scholar Author, Article, and Disclosure InformationAffiliations: St. George Hospital; Kogarah, Sydney, Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1997Volume 127, Issue 2Page: 163-164KeywordsBreast feedingDrug safetyDrugsLow molecular weight heparinPregnancyThromboembolism Issue Published: 15 July 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Twelve-year follow-up of a prospective randomized trial of hepatitis b recombinant DNA yeast vaccine versus plasma-derived vaccine without booster doses in children
Authors: Man-Fung Yuen, Wei-Ling Lim, Chi-Chung Cheng, Shiu-Kam Lam, Ching-Lung Lai
Journal: Hepatology (1999)

A total of 318 children were prospectively randomized in group 1 with two 5–μg doses of recombinant vaccine given at 0 and 1 month; in group 2 with three 5–μg doses of recombinant vaccine given at 0, 1, and 6 months; or in group 3 with three doses of plasma–derived vaccine given at 0, 1, and 6 months. Eleven subjects with a hepatitis B surface antigen antibody (anti–HBs) titer of less than 10 mIU/mL at 12 months were given an extra dose of vaccine and were excluded from analysis. No booster doses were given to any other subjects. All children were followed up yearly for the level of anti–HBs titers and for the detection of hepatitis B infection. At the 12th year of follow–up, there were significantly fewer subjects with anti–HBs of 10 mIU/mL or above in group 1 (60.4%) when compared with group 2 (81.4%; P = .0287) and group 3 (79.0%; P = .0381). The geometric mean titers (GMTs) of subjects of group 1 were significantly lower than those of group 2 and group 3 throughout the 12 years of follow–up. A total of 65 subjects had one or more episodes of anamnestic response. No subject became positive for hepatitis B surface antigen (HBsAg); 2 became positive for hepatitis B core antigen antibody (anti–HBc). In conclusion, the long–term protective immunity was better with three doses of hepatitis B vaccine (either the recombinant or plasma–derived) than with two doses. However, protection from hepatitis B infection could be equally achieved by either two doses or three doses of the vaccine. Booster doses were not necessary, probably because of effective anamnestic response.
Haemolysis in typhoid fever in children with G-6-PD deficiency.
Authors: C. Hersko, P. A. Vardy
Journal: BMJ (1967)

Evidence is presented that a cytopathic agent isolated from human nose, throat, and bronchial swabs, and termed " Ryan virus" is in fact an amoeba of the genus Hartmannella.Detection of a protozoal cell-type by electron microscopy led to the recognition of typical trophozoites and cysts of this free- living soil amoeba in inoculated tissue cultures.Details are given of cytopathic effects due to the amoebae, involving primarily the nuclei in cell cultures.It is probable that amoebae do occur in the nasopharynx in some patients with respiratory illness, and they should not necessarily be regarded as laboratory contaminants.Their clinical significance and pathogenicity for man are at present conjectural.
WHA calls for five demonstration projects on health research relevant to the developing world
Authors: A. Gulland
Journal: BMJ (2013)

The World Health Assembly has moved a step further to creating a global convention on stimulating research and development in the health problems of developing countries.

This week’s assembly agreed that the World Health Organization should establish a global health observatory to monitor and analyse relevant information on research and development. It also called for five health demonstration projects to fill research gaps that disproportionately affect developing countries. The assembly agreed that a meeting would take place before the end of 2013 to identify …
Re-entry due to manifest and concealed. His bundle ectopic systoles. Report of a case.
Authors: N El-Sherif, B Befeler, J Aranda, A Castellanos, R Lazzara
Journal: Circulation (1976)

Concealed (C) His bundle ectopic systoles (H') have been shown in man to give rise to first and second degree atrioventricular (A-V) block and to simulate nonconducted atrial premature beats (P'). This report outlines a hitherto undescribed electrophysiologic consequence of H' in a 69-year-old man with arteriosclerotic heart disease and a Wenckebach type second degree A-V block in the His-Purkinje system. During a His bundle study, H' were shown to conduct either to the atria and ventricles with varying relationships to P' and QRS, or to conduct only to the atria, simulating nonconducted P' or atrial fusion beats. Both types of H' could initiate a re-entrant arrhythmia during retrograde conduction. Of particular interest are late coupled H' that failed to conduct to the ventricles and also failed to activate the atria because of prior capture by the sinus impulse (CH'). These CH' could also initiate re-entry by conducting retrogradely to engage the subatrial re-entry circuit. Evidence is presented to suggest re-entry occurs by way of a retrograde concealed accessory pathway and antegrade conduction in the atrioventricular node.
Effect of combinations of drugs on all cause mortality in patients with ischaemic heart disease: nested case-control analysis
Authors: Julia Hippisley-Cox, Carol Coupland
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine the effect of combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors in the secondary prevention of all cause mortality in patients with ischaemic heart disease. <b>Design</b> Open prospective cohort study with nested case-control analysis. <b>Setting</b> 1.18 million patients registered with 89 general practices across 23 strategic health authority areas within the United Kingdom. Practices had longitudinal data for a minimum of eight years and were contributing to QRESEARCH, a new database. <b>Patients</b> All patients with a first diagnosis of ischaemic heart disease between January 1996 and December 2003. Cases were patients with ischaemic heart disease who died. Controls were patients with ischaemic heart disease who were matched for age, sex, and year of diagnosis and were alive at the time their matched case died. <b>Main outcome measures</b> Odds ratio with 95% confidence interval for risk of death in cases compared with controls. Exposure was current use of different combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors before death in cases, or the equivalent date in controls. <b>Results</b> 13 029 patients had a first diagnosis of ischaemic heart disease (incidence rate 338 per 100 000 person years). 2266 cases were matched to 9064 controls. Drug combinations associated with the greatest reduction in all cause mortality were statins, aspirin, and β blockers (83% reduction, 95% confidence interval 77% to 88%); statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors (75% reduction, 65% to 82%); and statins, aspirin, and angiotensin converting enzyme inhibitors (71% reduction, 59% to 79%). Treatments associated with the smallest reduction in all cause mortality were β blockers alone (19% reduction, 37% reduction to 4% increase), angiotensin converting enzyme inhibitors alone (20% reduction, 1% to 35%), and combined statins and angiotensin converting enzyme inhibitors (31% reduction, 57% reduction to 12% increase). <b>Conclusions</b> Combinations of statins, aspirins, and β blockers improve survival in high risk patients with cardiovascular disease, although the addition of an angiotensin converting enzyme inhibitor conferred no additional benefit despite the analysis being adjusted for congestive cardiac failure.
Abstract 228: Withaferin A downregulates tubulins and covalently binds β-tubulin at cysteine-303 in human breast cancer cells
Authors: Shivendra V. Singh, Marie Lue Antony, Joomin Lee, Eun-Ryeong Hahm, Su-Hyeong Kim, Guillermo Romero, Adam I. Marcus, Zhen Yang, Vandana Kumari, Xinhua Ji, Courtney L. Vowell, Peter Wipf, Guy T. Uechi, Nathan A. Yates
Journal: Cancer Research (2014)

Abstract We have shown previously that withaferin A (WA), a C5,C6-epoxy steroidal lactone derived from an Ayurvedic medicine plant (Withania somnifera), not only inhibits growth of human breast cancer cells in vitro and in vivo but also prevents mammary cancer development in a transgenic mouse model without any toxicity. However, the mechanisms underlying cancer preventive effect of WA are not fully understood. Herein, we report that tubulin is a novel target of WA in human breast cancer cells. WA treatment resulted in G2 and mitotic arrest in MCF-7 (estrogen-receptor positive), SK-BR-3 (estrogen-receptor negative), and SUM159 (triple-negative) cells in association with a marked decrease in protein level of β-tubulin. These effects were not observed with the naturally-occurring C6,C7-epoxy analogs of WA (withanone and withanolide A). In addition, a non-tumorigenic normal human mammary epithelial cell line (MCF-10A) was markedly more resistant to mitotic arrest and tubulin downregulation by WA treatment compared with breast cancer cells. Downregulation of tubulin protein in WA-treated cells was due to transcriptional repression as well as proteasomal degradation. Vehicle-treated control breast cancer cells exhibited a normal bi-polar spindle with chromosomes aligned along the metaphase plate. In contrast, WA treatment led to a severe disruption of the normal spindle morphology in breast cancer cells. Unlike breast cancer cells, WA-treated MCF-10A cells exhibited aggregation of tubulin around nucleus. NMR analyses revealed that the A-ring enone in WA, but not in withanone or withanolide A, was highly reactive with cysteamine and rapidly succumbed to irreversible nucleophilic addition. Mass spectrometry demonstrated direct covalent binding of WA at cysteine-303 of β-tubulin in MCF-7 cells. Molecular docking studies indicated that the WA-binding pocket was located on the surface of the β-tubulin and characterized by a hydrophobic floor, a hydrophobic wall, and a charge-balanced hydrophilic entrance. These results provide novel insights into the mechanism of anticancer effect of WA. This work was supported by the grants RO1 CA142604 and P30 CA047904 awarded by the National Cancer Institute. Citation Format: Shivendra V. Singh, Marie Lue Antony, Joomin Lee, Eun-Ryeong Hahm, Su-Hyeong Kim, Guillermo Romero, Adam I. Marcus, Zhen Yang, Vandana Kumari, Xinhua Ji, Courtney L. Vowell, Peter Wipf, Guy T. Uechi, Nathan A. Yates. Withaferin A downregulates tubulins and covalently binds β-tubulin at cysteine-303 in human breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 228. doi:10.1158/1538-7445.AM2014-228
A SIMPLIFIED CHEMOSTAT FOR THE GROWTH OF MAMMALIAN CELLS: CHARACTERISTICS OF CELL GROWTH IN CONTINUOUS CULTURE
Authors: Edward P. Cohen, Harry Eagle
Journal: The Journal of Experimental Medicine (1961)

A simplified technique has been described for the continuous growth of mammalian cells in suspension culture. The cell population density increased as the rate of input of fresh medium was decreased, and the average generation time was concommittantly prolonged. At relatively high input rates, the population remained stabilized for an indefinite period, but at low flow rates, there was sometimes a cyclical variation in population density. The factor limiting growth rate at input rates of approximately 0.2 volumes per day was not the exhaustion of the medium; but in some experiments a non-dialyzable material appeared which inhibited cell growth.
Induction of Interleukin-6 Synthesis in the Myocardium
Authors: Gilbert L. Kukielka, C. Wayne Smith, Anthony M. Manning, Keith A. Youker, Lloyd H. Michael, Mark L. Entman
Journal: Circulation (1995)

Background Neutrophil-induced injury of myocardial cells requires the expression of intercellular adhesion molecule-1 (ICAM-1) on the myocyte surface and is mediated by ICAM-1–CD11b/CD18 adhesion. We have previously shown that interleukin-6 (IL-6) cytokine activity, present in cardiac lymph, induces ICAM-1 on isolated cardiac myocytes. Furthermore, in previous in vivo studies, we have also shown ICAM-1 mRNA induction in the myocardium within the first hour of reperfusion in the previously ischemic viable zone. We hypothesized that induction of IL-6 synthesis in the myocardium was an integral part of the reaction to injury resulting from ischemia and reperfusion and was associated with induction of ICAM-1 on myocardial cells. Methods and Results In this study, cloned canine IL-6 cDNA was used as a molecular probe to study the regulation of IL-6 in an awake canine model of myocardial ischemia and reperfusion. IL-6 mRNA was induced in ischemic and reperfused segments of myocardium preferentially in segments previously exposed to severe ischemia. Peak levels of IL-6 mRNA were reached within 3 hours of reperfusion. At the same time, IL-6 mRNA and ICAM-1 mRNA were found in the same myocardial segments. In contrast to hearts that were ischemic for 1 hour and reperfused for 3 hours, nonreperfused hearts after 4 hours of persistent ischemia demonstrated minimal induction of ICAM-1 or IL-6 despite similar degrees of injury and blood flow reductions during ischemia. After 24 hours of persistent ischemia, levels of IL-6 mRNA were comparable to those observed in hearts that were ischemic for 1 hour and subsequently reperfused for 24 hours. Conclusions Our results demonstrate induction of IL-6 mRNA in the myocardium and that this synthesis is accelerated by reperfusion. Evidence is also provided to show that peak IL-6 mRNA precedes that of ICAM-1 mRNA. These findings are compatible with our hypothesis that IL-6 is important in the induction of ICAM-1 in the area of ischemia. In addition, these studies suggest that the necessary factors to promote adhesive interactions between transmigrated neutrophils and cardiac myocytes are present in reperfused myocardium.
Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction?
Authors: D A Street, G W Comstock, R M Salkeld, W Schüep, M J Klag
Journal: Circulation (1994)

BACKGROUND In vitro, animal and epidemiological studies suggest that lipoprotein oxidation may play an important role in atherosclerosis. Antioxidants may protect against lipoprotein oxidation and in that way inhibit atherosclerosis and its clinical sequelae. To investigate this possibility, we examined the association between levels of several antioxidants and myocardial infarction using serum specimens collected 7 to 14 years before the onset of myocardial infarction. METHODS AND RESULTS A nested case-control design was used. Cases and control subjects were selected from the 25,802 persons who had donated 15 mL of blood in 1974 for a serum bank. Cases comprised 123 persons with a subsequent first diagnosis of myocardial infarction who ranged from 23 through 58 years of age in 1974 and who had had their first diagnosis of myocardial infarction during 1981 to 1988. Two groups of control subjects matched to the cases for sex and age were selected from donors to the serum bank, one from those with hospital admissions during the same period and the other from the total group of donors. Sera were assayed for four carotenoids (beta-carotene, lycopene, lutein, and zeaxanthin), alpha-tocopherol, and cholesterol. Because associations with these serum nutrients showed similar trends whether based on hospital or community controls, the two control groups were combined. There was a significantly increasing risk for subsequent myocardial infarction with decreasing levels of beta-carotene in 1974 (P value for trend, .02) and a suggestive trend with decreasing levels of lutein (P = .09). When the results were stratified by smoking status, the excess risk of myocardial infarction associated with low serum levels of carotenoids was limited to smokers. A protective association with higher levels of alpha-tocopherol was suggested only among persons with high levels of serum cholesterol. CONCLUSIONS Low serum levels of carotenoids were associated with an increased risk of subsequent myocardial infarction among smokers.
Nosocomial Acinetobacter baumannii Infections: Microbiological and Clinical Epidemiology
Authors: Daniel Villers
Journal: Annals of Internal Medicine (1998)

Background: Acinetobacter baumannii is an important opportunistic pathogen that is rapidly evolving toward multidrug resistance and is involved in various nosocomial infections that are often severe. It is difficult to prevent A. baumannii infection because A. baumannii is ubiquitous and the epidemiology of the infections it causes is complex. Objective: To study the epidemiology of A. baumannii infections and assess the relation between fluoroquinolone use and the persistence of multidrug-resistant clones. Design: Three case–control studies and a retrospective cohort study. Setting: A 20-bed medical and surgical intensive care unit. Patients: Acinetobacter baumannii was isolated from 45 patients in urine (31%), the lower respiratory tract (26.7%), wounds (17.8%), blood (11.1%), skin (6.7%), cerebrospinal fluid (4.4%), and sinus specimens (2.2%). One death was due to A. baumannii infection. Measurements: Antimicrobial resistance pattern and molecular typing were used to characterize isolates. The incidence of A. baumannii infection and the use of fluoroquinolones were calculated annually. Results: Initially, 28 patients developed A. baumannii infection. Eleven isolates had the same antimicrobial susceptibility profile, genotypic profile, or both (epidemic cases), and 17 were heterogeneous (endemic cases). A surgical procedure done in an emergency operating room was the main risk factor for epidemic cases, whereas previous receipt of a fluoroquinolone was the only risk factor for endemic cases. The opening of a new operating room combined with the restriction of fluoroquinolone use contributed to a transitory reduction in the incidence of infection. When a third epidemiologic study was done, previous receipt of a fluoroquinolone was again an independent risk factor and a parallel was seen between the amount of intravenous fluoroquinolones prescribed and the incidence of endemic infection. Conclusion: Epidemic infections coexisted with endemic infections favored by the selection pressure of intravenous fluoroquinolones.
CHLORAMPHENICOL AND APLASTIC ANEMIA
Authors: Jack J. Rheingold
Journal: JAMA (1952)

Since chloramphenicol is an efficient broad spectrum antibiotic that is widely used, the possibility that it may be the cause of hematological disorders is, naturally, a serious one. Recently, five cases of fatal aplastic anemia have come to our attention. In each instance, we believe chloramphenicol to be etiologically implicated. It is our purpose to report these cases and to review the literature on hematological disorders believed to be caused by this drug. <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> A 31-year-old housewife had received phenobarbital and atropine intermittently for over a year because of nervousness. In December, 1951, an upper respiratory tract infection developed, and she was given a total of 15 capsules of chloramphenicol. Early in January, 1952, she received an additional six capsules. On this occasion, urticaria developed over the lower extremities and lasted for several days. No other recent history of exposure to drugs or toxic agents could
Abstract P3-01-04: Obesity induces functional transcriptomic changes enhancing the cancer hallmarks of estrogen receptor-positive breast cancer
Authors: E Fuentes-Mattei, L Phan, G Velazquez-Torres, F Zhang, P-C Chou, J-H Shin, H-H Choi, J-S Chen, J Chen, C Gully, C Carlock, R Zhao, Y Qi, Y Zhang, Y Wu, FJ Esteva, Y Lou, WL McKeehan, JE Ensor, GN Hortobagyi, L Pusztai, WF Symmans, M-H Lee, S-CJ Yeung
Journal: Cancer Research (2013)

Abstract Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor-positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon. Transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients were analyzed. A transgenic and an orthotopic/syngeneic obese mouse models were created to phenocopy obese patients and evaluate the effect of obesity on breast carcinogenesis and tumor progression, and to explore further direct mechanisms. Functional transcriptomic analysis of untreated human ER+ breast cancer revealed that obesity was associated with increased insulin signaling among others. Many of the functional changes in obese patients were linked to cancer hallmarks. Obese mouse models recapitulated the functional transcriptomic landscape of obesity-associated changes seen in human ER+ breast cancer and demonstrated the role of the Akt/mTOR pathway in obesity-induced breast carcinogenesis and tumor progression. Functional transcriptomic analysis identified 85 biological functions common to humans and mice. An in vitro co-culture model revealed that adipocyte-secreted adipokines (e.g., TIMP-1) regulate adipocyte-induced breast cancer cell proliferation and invasion. The human transcriptomic data provided direct evidence for the roles of hyperinsulinemia, estrogen signaling, adipokine secretion, and inflammation in the link between obesity and ER+ breast cancer. Our animal experiments provide strong evidence for the causal relationship between obesity and accelerated carcinogenesis and cancer progression and for potential therapeutic interventions by blocking these signaling pathways. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-01-04.