tbuckley/cabot-search huggingface dataset:
Comparative effects of estrogen testosterone and progesterone on benign mammary tumors of the rat.
Authors: Jacob Heiman
Journal: Cancer Research (1943)

This paper deals with the effects of progesterone on mammary tumors and compares the effects of estrogen androgen and progesterone injected singly or in combination.  Intact and castrated male and female rats with spontaneous benign tumors or auto- or homotransplants were injected with progesterone.  The dosage varied between 9-18 mgm of progesterone and 1-2.5 mgm of estrogen.  Progesterone inhibited the growth of the adenomatous portion of spontaneous rat mammary fibroadenoma; shrinkage was followed by fibrosis.  Progesterone reduced the percentage of takes of auto- and homotransplants (66-22%).  18 mgm of progesterone did not interfere with the stimulating effect of 2.5 mgm of estrogen however 18 mgm of progesterone inhibited the stimulating effect of 1 mgm of estrogen.  Progesterone did not affect fibromas growing in castrated females or normal males.  Progesterone alone inhibited growth of the glandular portion of adenofibromas in castrated males.  Progesterone and testosterone in combination were effective in reducing the percentage of takes (66.6-8.3%) and in inhibiting the growth of the glandular fraction of the tumor.  Large doses of progesterone and testosterone were necessary to neutralize the stimulating effect of estrogen on growing fibroadenoma.  Rat fibroma myxoma and sarcoma were not inhibited by progesterone.  Progesterone did not hinder the growth of fibroadenomas in pregnant rats because of the high estrogen content of the organism.  The action of progesterone on benign mammary fibroadenomas was unlike the progestational effect on the uterus and normal mammary glands.
For neurosciences, proposals are "too little too late"
Authors: A. Mcevoy, M. Smith, N. Kitchen, M. Powell
Journal: BMJ (1996)

Finally, Waugh suggests that photography might be added to screening by opticians and be carried out by opticians.This would probably incur an additional fee and is unlikely to be any more cost effective, and is more likely to be less comprehensive, than a system based on the practice register and recall and directly involving the primary care team.
Abstract 2390: Düsseldorfer-ABCD Trial (Autologous Bone Marrow Cells in Dilated Cardiomyopathy)
Authors: Christiana M Schannwell, Muhammad Yousef, Carmen M Basalyk, Tobias Zeus, Michael Brehm, Matthias Köstering, Bodo-Eckehard Strauer
Journal: Circulation (2008)

Heart failure is a dangerous disease with an increasing frequency. Although conventional drug therapy may delay remodeling, there is no basic therapeutic regime available for preventing or even reversing this process. Several preclinical as well as clinical trials have shown that transplantation of autologous bone marrow cells improved cardiac function after myocardial infarction and chronic heart disease (CAD). We investigated the effects of intracoronary (ic) autologous stem cell transplantation (STX) at patients with non-ischemic dilated cardiomyopathy (DCM). Methods: A total of 10 patients with DCM were included in this study (group I). The control group also consists of 10 age and sex-matched patients with comparable ejection fraction (group II). CAD and myocarditis were excluded. All patients of group I received an ic autologous STX with mononuclear cells. Cell transplantation was performed via the ic administration route. All cells were infused directly into the dominant coronary vessel. To achieve a maximal ischemic stimulus all patients received Dobutamine intravenously and Dipipyridamol by ic application. All 20 patients were re-investigated after 3 months. Results: Three months after ic STX, the global left ventricular ejection fraction increased in patients from 18 ± 1 up to 26 ± 3% (p &lt; 0.01). In parallel the physical ability (functional capacity) rose from 25 to 75 watt (p &lt; 0.01). In addition, we found an improvement of maximum oxygen uptake under stress from 1236 ± 217 up to 1473 ± 198 ml/min (p &lt; 0.01). Furthermore we documented a reduction of arrythmia. An unchanged or even impaired left ventricular function was not observed in any patient of group I. In the control group (group II) no significant changes were documented. No side effects of ic autologous STX were found, particularly no arrythmias, no heart insufficiency, no dyspnoea and no palpitations. Conclusion: These results show that transplantation of autologous bone marrow cells, as well as the ic approach, represents a novel and effective therapeutic procedure for the therapy of DCM. For this method of therapy, no ethical problems exist, and no side effects were observed. However, further experimental studies and controlled prospective clinical trials have to follow.
Abstract 13023: Pre-Operative Left Ventricular Ejection Fraction and Long-term Survival After Aortic Valve Replacement
Authors: Joseph DeSimone, Meredith Sorensen, Anthony DiScipio, Bruce Leavitt, Robert Kramer, Lawrence Dacey, Todd MacKenzie, William Nugent, Donato Sisto, Robert Helm, Gerald Sardella, Francis DiPierro, Yvon Baribeau, Cantwell Clark, Robert Groom, Stephen Surgenor, Cathy Ross, Elaine Olmstead, David Malenka, Donald Likosky
Journal: Circulation (2010)
Cardenolides: old drugs with new applications in oncology.
Authors: Robert Kiss, Tatjana Mijatovic, Eric Van Quaquebeke, Francis Darro
Journal: Cancer Research (2006)

5453  Cardiac glycosides (to which belongs a class of drugs named cardenolides) have been used for centuries for treating heart failure. Digoxin, which is obtained from Digitalis lanata, is the most commonly prescribed form of cardiac glycoside because it is orally active. A number of reports have already emphasized the potential roles of cardiotonic steroids as valuable anti-cancer agents, as for example by Stenkvist for breast cancer patients (Anti-Cancer Drugs 2001). An ethanolic extract of Nerium oleander enriched in oleandrin (Xenavex) is now entering Phase I/II clinical trials. We discovered a new cardenolide (2”-oxovoruscharin) in an African plant (Van Quaquebeke et al., J Med Chem 2005). The acute maximal tolerated dose (MTD) in mice for 2“-oxovorusharin is similar to those acute MTDs observed for other cardiac glycosides like ouabain, digitoxin and oleandrin, i.e. ranging between 5 and 10 mg/kg, and leading therefore to weak in vivo therapeutic indices. We succeeded, by means of medicinal chemistry, in reducing by more than ten times this MTD index for 2”-oxovorusharin while keeping its exceptional anti-tumor activity intact, thus increasing by ten times the potential therapeutic index of this new hemisynthetic compound that we named UNBS1450 (Van Quaquebeke et al., J Med Chem 2005). We detail here the in vivo data obtained with this compound in 11 human xenograft models (5 subcutaneous and 6 orthotopic) from 8 histological types. UNBS1450-induced anti-tumor activity was analyzed in terms of tumor growth inhibition in the case of subcutaneous xenograft models and in terms of increase in the survival periods of tumor-bearing immunodeficient mice in the case of orthotopic xenograft models. The active in vivo doses used for chronic treatment with UNBS1450 ranged between 5 and 10 mg, i.e. below one tenth of the MTD value. UNBS1450 was active i.p., i.v. and orally. UNBS1450 was more active than taxol, oxaliplatin and irinotecan in NSCLC xenografts, than mitoxantrone in prostate xenografts and than temozolomide in glioblastoma xenografts. UNBS1450 was as active as adriamycin and irinotecan in breast and melanoma xenografts respectively. UNBS1450 was either weakly or not active in head and neck and pancreas cancer xenografts. UNBS1450 significantly synergized the anti-tumor effects of irinotecan in an orthotopic colon cancer xenograft. The general mechanism of action that can be associated with the UNBS1450-mediated anti-tumor effects relates to the disorganization of the actin cytoskeleton occurring through the binding of UNBS1450 to the sodium pump at the cellular membrane, a process that generates a sustained increase in intracellular calcium concentration. UNBS1450 can thus be considered an anti-migratory (because the actin cytoskeleton is essential for cancer cell migration) and a cytostatic (because the actin cytoskeleton is essential during cytokinesis) drug.
Abstract 5081: Circulating Microparticles as Potential Biomarkers for Primary Intracerebral Hemorrhage Stroke
Authors: Shuzhen Chen, Dongsheng Zhang, Wenfeng Zhang, Jinju Wang, Yigang Wang, Yanfang Chen
Journal: Circulation (2009)

Introduction: Primary intracerebral hemorrhage (ICH) stroke is a serious complication of uncontrolled hypertension. Recent clinical studies have shown that circulating microparticles (MPs) from endothelia (EMPs), platelets (PMPs) and endothelial progenitor cells (EPC-MPs) are potential biomarkers for cardiovascular diseases. However, the role of circulating MPs in ICH stroke is unknown. Methods and Results: The human renin and angiotensinogen transgenic (R+A+) and the control (R−A−) mice (male, 8 –10 weeks) were fed with normal diet or high salt diet (8% NaCl, HSD) plus nitric oxide synthase inhibitor L-NAME (120 mg/kg/day) in drinking water for two weeks. Mean arterial pressure (MAP) was measured using telemetric probes. Circulating MPs were identified by membrane markers, CD62E (for EMPs), CD62P (for PMPs), and CD34 and VEGFR2 (for EPC-MPs) using flow cytometry. The severity of ICH was determined by histological analysis of total bleeding area. The lumen/wall in the middle cerebral artery (MCA) was histologically measured. Results (Table and Figure ) showed: The R+A+ mice were hypertensive and had higher basal level of circulating PMPs and EMPs with no difference in EPC-MPs; After fed with HSD and L-NAME, R+A+ mice had severe hypertension and 50% of them developed ISH stroke within two weeks; There was a further increase of EMPs and a decrease of EPC-MPs in R+A+ mice with ICH stroke; There were strong correlations of EMPs (r=0.44~0.61) and EPC-MPs (r=−0.52~0.78) with MAP, MCA lumen/wall and total area of bleeding sites. Conclusion: Circulating EPC-MPs and EMPs could serve as useful biomarkers for uncontrolled hypertension, MCA remodeling and ICH stroke. Table. Blood pressure, circulating MPs and MCA lumen/wall in R+A+ and R−A− mice fed with normal diet or HSD and L-NAME for two weeks Fig. Hemorrhages in the brain (A, D: brainstem: B, E: cerebellum; C,F: basal ganglia) and MCA remodeling, A–C; R+A+ mice fed with HSD+L-NAME; D–F: R−A− mice fed with HSD+L-NAME; G: R−A− mice fed with normal diet, H: R−A− mice fed with HSD+L-NAME; I: R+A+ mice fed with HSD+L-NAME
Biomarker-driven drug discovery: Identification and characterization of small molecule inhibitors against beta-catenin and Aurora kinase
Authors: Paul E. Young, Steve Horrigan, Daniel Soppet, Martin Shea, Staszek Pikul, Tamara Tatunchak, Tammy Lawrence, Kathryn Strand, Marion Chakiath, Juana Castaneda, Jeff Watthey, Jeff Strovel, Stephen Glanowski, Qin Zong, Derong Liu, Gene Ohler, Zoe Weaver, Pachai Natarajan, Anna Glodek
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1358 

RNAi-induced inhibition of beta-catenin or Aurora kinase is associated with specific changes in gene expression in treated cells. Biomarker-driven drug discovery is a systems biology approach that uses such changes in gene expression as screening signatures to identify small molecule inhibitors of these same targets. We have successfully completed independent screens of small molecule libraries against beta-catenin and Aurora kinase signatures using this approach and have discovered a number of active compound families. We have systematically analyzed these hit compounds with a number of relevant secondary assays, in order to identify the most promising candidates from each program for lead selection and optimization. We will demonstrate that this discovery approach yields hit compounds that can inhibit multiple, distinct nodes within each pathway.
Abstract 13902: Aberrant Sialylation Modulates Cardiac Excitability and Conduction
Authors: Andrew R Ednie, Kofi-Kermit Horton, Hui Yang, Jiashin Wu, Eric S Bennett
Journal: Circulation (2011)

We recently showed that regulated changes in the cardiac glycome result in voltage-gated Na+ channels that are less sialylated as well as in altered cardiomyocyte INa and action potential (AP) wave...
Abstract 27: Effects of Early Initiation of Induced Therapeutic Hypothermia
Authors: Francisco Castelblanco
Journal: Circulation (2011)

Cardiac arrests are responsible for about 325,000 deaths annually in the United States (Heart Rhythm Foundation, 2010). The majority of these cardiac arrests occur outside the hospital setting, with a dismal national survival rate of 8% (American Heart Association, 2010). The Bernard (2002) and HACA (2002) studies demonstrated that by initiating therapeutic hypothermia as a treatment modality for cardiac arrests the survival rate could be as high as 49% and 55% respectively. Therapeutic hypothermia can be initiated in many different settings. The question remains, does the setting of the initiation of therapeutic hypothermia effect patient outcomes? The purpose of this study was to compare the effects of initiation of therapeutic hypothermia by EMS, Emergency Departments, and ICU nurses on cardiac arrest patient outcomes as measured by the Glasgow Coma Scale at discharge. This study utilized a convenience sample of 178 consecutive cardiac arrest patients admitted from 2008-2010 in an 800-bed hospital in Western North Carolina. From the overall sample, 57 patients had a favorable neurological outcome (32% overall survival rate). EMS initiated therapeutic hypothermia in 24 instances with 7 patients surviving to discharge (29% survival rate). The Emergency Department initiated therapeutic hypothermia in 17 instances with 8 patients surviving to discharge (47% survival rate). ICU nurses initiated therapeutic hypothermia in 137 instances with 42 patients surviving to discharge (31% survival rate). Study results reproduced previous findings demonstrating the efficacy of therapeutic hypothermia in the treatment of cardiac arrests. The results also indicate a possible advantage to the initiation of therapeutic hypothermia by Emergency Departments.
ADVANTAGES OF PROZINSULIN (PROTAMINE ZINC INSULIN) THERAPY: DIETARY SUGGESTIONS AND NOTES ON THE MANAGEMENT OF CASES
Authors: Herbert Pollack, Henry Dolger
Journal: Annals of Internal Medicine (1939)

Article1 June 1939ADVANTAGES OF PROZINSULIN (PROTAMINE ZINC INSULIN) THERAPY: DIETARY SUGGESTIONS AND NOTES ON THE MANAGEMENT OF CASESHERBERT POLLACK, HENRY DOLGERHERBERT POLLACKSearch for more papers by this author, HENRY DOLGERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-12-2010 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptProzinsulin is being used in the routine control of the diabetic state. Difficulties have been encountered in a certain group of patients with this type of therapy. This group corresponds in part to the same group who had their difficulties with the old insulin. The purpose of this paper is to present a method, applicable in particular to the control of the unstable case. In addition, it is felt that the regime can be used with advantage in treating other diabetic patients. The successful change to Prozinsulin is dependent upon a complete rearrangement of the diet.The physiological necessity for... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*"Prozinsulin" is offered as a convenient contraction of "Protamine Zinc Insulin."Received for publication April 21, 1938.From the Diabetic Clinic (H. Lande), the Medical Services, and the Division of Laboratories at the Mount Sinai Hospital, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDietary management of diabetes mellitus“Simple” Obesity: A Current Review 1 June 1939Volume 12, Issue 12Page: 2010-2021KeywordsDietInsulinMedical servicesProtaminesZinc ePublished: 1 December 2008 Issue Published: 1 June 1939 PDF downloadLoading ...
Abstract 17805: Efficacy of Collateral Circulation in Patients with Acute Coronary Syndrome Treated with Primary Percutaneous Coronary Intervention
Authors: Tomoyo Sugiyama, Shigeki Kimura, Hiroshi Inagaki, Shunji Yoshikawa, Go Haraguchi, Hiroyuki Hikita, Atsushi Takahashi, Mitsuaki Isobe
Journal: Circulation (2011)

Background: Collateral circulation has been reported to be related to a better outcome in patients with coronary artery disease. However, the efficacy of collateral circulation remains unclear in patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Method: We investigated 139 patients with ACS (acute myocardial infarction; n=108, unstable angina; n=31) who underwent primary PCI. We divided the patients into two groups according to the formation of collateral circulation; patients with rich collateral (Rentrop grade 2-3) (rich-coll) and with poor collateral (Rentrop grade 0-1) (poor-coll). Baseline characteristics, intravascular ultrasound (IVUS) and angiographical findings including TIMI flow, corrected TIMI frame counts (CTFCs) and myocardial blush grades (MBG) were examined. The efficacy of collateral circulation was evaluated according to the antegrade coronary flow grade of each lesion. Result: Thirty-four patients (24.5%) had rich collateral circulation. In patients with occluded culprit arteries (initial TIMI flow 0-1, n=74), rich-coll patients (n=26, 35.1%) had a significantly higher CK levels on admission (969±1249 IU/l vs. 225±421 IU/l, p=0.0003), greater plaque volume of necrotic-core (NC) by IVUS (60.6±32.2 mm 3 vs. 42.7±32.8 mm 3 , p=0.05) and a higher frequency of transient slow-flow phenomenon during PCI than poor-coll patients (38.5% vs. 16.7%, p=0.049). However, outcomes after PCI were similar among the groups (final CTFC&gt;27; 44.0% vs. 42.6%, p=1.00, MBG 0-1; 57.7% vs. 56.3%, p=1.00 and max CK levels; 3337±2864 IU/l vs. 4147±3337 IU/l, p=0.30). On the other hand, in patients with non-occluded culprit arteries (TIMI flow 2-3, n=65), rich-coll patients (n=8, 12.3%) showed a tendency of better outcome after PCI including coronary flow (final CTFC&gt;27; 0.0% vs. 29.8%, p=0.099) and myocardial perfusion (MBG 0-1; 0.0% vs. 24.6%, p=0.18), although CK levels on admission (187±122 IU/l vs. 258±289 IU/l, p=0.50) and NC volume by IVUS (41.4±42.6 mm 3 vs. 36.6±28.5 mm 3 , p=0.69) were similar. Conclusion: In ACS patients, the existence of rich collateral circulation might reduce the influences of several risk factors including IVUS findings on worse outcomes after PCI.
...and south Wales
Authors: A W Davies, J R York, S R Jones
Journal: BMJ (1995)

Scare over oral contraceptivesEffect on behaviour ofwomen attending a family planning clinic EDrTOR,-The Department of Health's recent press release concerning the safety of some third generation contraceptive pills has important consequences for women using oral contraception.I To document their views and any change in behaviour of women taking the contraceptive pill after this warning, a survey was carried out at a large family planning clinic.After the announcement a telephone helpline was established at the clinic.This took 2348 calls on the first seven days, and the number of attendances rose from an expected 700 to 2029 in that week.One week later a piloted questionnaire was given to a representative sample of women before consultation over six days.A response rate of 71% was obtained (n=274).The age range was 14-54, with 50 women under 20 and 58 over 30.The table gives the women's views.Those who were and those who were not using oral contraception differed in terms of their awareness of the announcement (177 (99%) v 85 (89%) were aware of it) although not in the belief that the announcement was a reasonable method ofinforming women (97 (54%) v 50 (52%/0)).The behaviour of the 178 women taking the pill was examined.Altogether 141 were taking a
Diverting attention from financial conflicts of interest
Authors: J. Lenzer, S. Brownlee
Journal: BMJ (2015)

Godlee’s comment that “there is little dispute that non-financial conflicts of interest—such as academic passion and personal belief—are just as important [as], if harder to track” than financial conflicts, begs examination for two reasons.1

Firstly, personal biases are generally, although not always, multidirectional; some experts might prefer one approach to patient care for personal or philosophical reasons, or may believe fervently in a …
Abstract 837: Beta1 And Beta2 Adrenergic Receptor Transgenic Mice Display Distinct MicroRNA Expression Patterns That Converge On The Hypertrophic Signature
Authors: Danish Sayed, Shweta Rane, Leng-Yi Chen, Minzhen He, Jacqueline Lypowy, Stefan Engelhardt, Lin Yan, Dorothy Vatner, Junichi Sadoshima, Maha Abdellatif
Journal: Circulation (2007)

MicroRNA (miRNA) are ~22 ribonucleotides-long, with a potential to recognize multiple mRNA targets guided by sequence complimentarity. This class of molecules is functionally versatile, with the capacity to specifically inhibit translation, as well as, induce mRNA degradation, through targeting the 3′-untranslated regions. The levels of individual miRNA vary under different developmental, biological, or pathological conditions, thus, implicating them in normal and pathological cellular attributes. We have previously reported a miRNA signature that distinguishes pressure-overload compensatory hypertrophy by recapitulating the neonatal pattern. We hypothesized that this ’signature’ might aid in discriminating the underlying molecular differences in genetic models of cardiac hypertrophy, as seen in the beta1 and 2 adrenergic receptor (B1AR and B2AR) transgenic (Tg) mice. To address this, we used microarray analysis of RNA isolated from the hearts of 3 months old B1AR and B2AR mice. In general, while both mice exhibited an overlap with the hypertrophy signature including, upregulation of miR-21 and downregulation of miR-133a, miR-133b, and miR-185, the B2-AR Tg exhibited a more extensive overlap with the hypertrophy pattern, which further included upregulation of miR-199a*, miR-214, and miR-15b. To understand the functional significance of these miRNA in myocyte hypertrophy, we cloned them and their anti-sense sequences into adenoviral vectors. Significantly, over-expression miR-21 resulted in a, dose-dependent, branching (sprouting) of the cells. Computational predictions by ’TargetScanS’ identified sprouty as potential target. Subsequently, we confirmed down-regulation of sprouty by over-expression of miR-21 and vice versa. Sprouty is a known inhibitor of the Ras-MAPK signaling pathway and is, concordantly, downregulated in many forms of cancer. In the heart, sprouty has been suggested to control myocyte size and vascularization during cardiac hypertrophy. Thus, we propose that B1AR and B2AR Tg models exhibit distinct miRNA profiles that converge on that of pressure-overload cardiac hypertrophy. Moreover, the commonly over-expressed miR-21 plays a role in downregulating sprouty, an antagonist of the Ras-MAPK pathway.
Ongoing outbreak of dengue type 1 in the Autonomous Region of Madeira, Portugal: preliminary report
Authors: C A Sousa, M Clairouin, G Seixas, B Viveiros, M T Novo, A C Silva, M T Escoval, A Economopoulou
Journal: Eurosurveillance (2012)

Following the identification of two autochthonous cases of dengue type 1 on 3 October 2012, an outbreak of dengue fever has been reported in Madeira, Portugal. As of 25 November, 1,891 cases have been detected on the island where the vector Aedes aegypti had been established in some areas since 2005. This event represents the first epidemic of dengue fever in Europe since 1928 and concerted control measures have been initiated by local health authorities.