tbuckley/cabot-search huggingface dataset:
Abstract B60: Overcoming drug resistant cancer by hyaluronic acid based nanogel formulated with anticancer drugs
Authors: Xin Wei, Thulani H. Senanayake, Serguei V. Vinogradov
Journal: Clinical Cancer Research (2012)

Abstract One of major challenges of current anticancer therapies is the overcoming of emerging drug resistances and the preventing of tumor relapse. Among different causes of tumor resistance to therapy, the most important is probably the presence of a population of cancer initiating/stem cells (CSC) distinguished from other cancer cells by low metabolic activity, protective apoptotic signaling pathways and overexpression of drug efflux transporters [1, 2]. Many drug-resistant tumors and CSC display the overexpressed levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA) [3]. The HA-CD44 interaction plays a prominent part in mediating cellular and intercellular events during cancer development. For biomedical applications, HA has been actively studied as a scaffold for tissue engineering and targeting moiety for drug delivery [4]. Here, we report an advanced design of HA-based polymeric nanogel-drug formulations with stronger activity compared to free drugs, which can potentially target CD44-expressing drug-resistant tumor cells. The novel nanogels are based on the biocompatible and biodegradable HA-drug conjugates with a high drug load and linked hydrophobic moieties (e.g., cholesterol), which are capable of folding into nanogels in aqueous media. A set of nanogel conjugates of poorly soluble anticancer drug, including curcumin, etoposide and salinomycin, was obtained, characterized and studied in cancer cell cultures. Cholesterol is a common cellular component that was expected to facilitate nanogel-membrane interaction and the intracellular transport of these drugs. The drug content in nanogel conjugates was as high as 15–20% (NMR analysis). These nanogels formed very small and uniform particles of 30–40 nm in diameter as determined by dynamic light scattering. The small size of nanogels can facilitate passive tumor accumulation through leaky neovasculature (EPR effect) and drug distribution in tumor tissue. Cytotoxicity assays (MTT) demonstrated stronger anticancer activity of nanogel-drug conjugates compared to free drugs and HA-drug conjugates in human breast carcinoma cells in vitro. Fluorescent microscopy confirmed that these nanogels are internalized by receptor-mediated endocytosis depending on the expression of CD44 receptors on the surface of cancer cells. Potential further developments would include an optimization of the hydrophilic-lipophilic balance of these nanogel-drug conjugates, introduction of diagnostic and vector molecules, and the development of dual-drug nanoformulations. In conclusion, we developed and characterized in vitro a novel HA-based nanogel drug delivery and theranostic platform that exhibits high anticancer activity and has a potential to become a novel therapy for overcoming tumor drug resistance.
Resuscitation and Function of the Cadaver Heart
Authors: ROBERT D. WUERFLEIN, NORMAN E. SHUMWAY
Journal: Circulation (1967)

Cadaver dog hearts with anoxia for one and one-half hours and no cooling were revived with 70% (18 of 26) success. There was occasional success after one and one-half to two hours of anoxia. At two hours no heart could be revived. After resuscitation cadaver hearts were maintained in a functional heart-lung preparation for periods up to 30 hours. Attempts were made to transplant ten of these hearts into the orthotopic position. There were no long-term survivors; all ten, however, were able to take over the circulatory load after bypass. Four dogs maintained an adequate circulation without supportive drugs for from eight to 38 hours.
Suppressor cells may help prevent fetal rejection
Authors: William Check
Journal: JAMA (1978)

Since the discovery early in this century that the body's immune system is capable of initiating the rejection of foreign cells, there has been continuing speculation about why the fetus is exempt from this reaction. Suggestions that the placenta prevents passage of antigenic material between the mother and fetus have been disproved, and it is now known that fetal and maternal cells are exchanged through the placenta and that both humoral and cellular immunity to fetal antigens develop in the mother. Recently, in an attempt to find out whether the normal immunity of such women might be in some way blocked, J. B. Dossetor, MD, PhD, professor of medicine and director of the transplant research laboratory, and T. Kovithavongs, MD, assistant professor of medicine, both of the University of Alberta in Edmonton, looked for the presence of suppressor cells in the blood of multiparous women. They found that multiparous women
Stroke victim's case highlights legal confusion
Authors: C Dyer
Journal: BMJ (1994)

The High Court in London has been asked to intervene in a battle over the future of a wealthy stroke victim between his estranged wife and son in Norway and his cohabitee in England. The 75 year old international photographer, named only as Mr S, who suffered a massive stroke a year ago, is being cared for in an English hospital pending the outcome of the wrangle over where he should live.

His estranged wife, from whom he separated in 1945, and his son want him transferred to a nursing home in Norway, while the Englishwoman with whom he has lived for four years wants …
Lack of effect of drinking water chlorine on lipid and thyroid metabolism in healthy humans.
Authors: R G Wones, C C Deck, B Stadler, S Roark, E Hogg, L A Frohman
Journal: Environmental Health Perspectives (1993)

Animal studies and a single human epidemiological study have suggested that chlorine in drinking water may raise the level of blood cholesterol. The purpose of this study was to determine whether a 4-week exposure to drinking water chlorine (1.5 L per day) at a concentration of 20 ppm (ppm = mg/L) under controlled conditions would alter circulating parameters of lipid metabolism in healthy humans. Thirty men and thirty women each completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. For the first 4 weeks of the protocol, all subjects consumed distilled water. For the second 4 weeks, half of the subjects were assigned randomly to drink 1.5 L per day of chlorinated water (20 ppm), while the others continued drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Compared to the control group, those subjects given chlorine showed no significant changes in total plasma cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, or apolipoproteins A1, A2, or B. There was a trend toward low serum thyroxine and triiodothyronine levels in men given chlorine, though thyroid-stimulating hormone levels were unchanged. This trend, if real, was not clinically significant. Thus, short-term exposure to chlorinated drinking water at 20 ppm appears to have no significant impact on parameters of lipid or thyroid metabolism in healthy humans.
Quick Reference to Clinical Nutrition: A Guide for Physicians
Authors: Albert I. Mendeloff
Journal: JAMA (1988)

This is the second edition of a paperback originally published in 1979. That first volume enlisted the assistance of 36 contributors to produce 27 chapters, 389 pages, and a long but somewhat incomplete index. There were a number of overlapping sections, as is inevitable in a text surveying nutritional aspects of many different disorders, and there were typographical errors, but the original volume was well produced and generally easy to use. The new second edition utilizes contributions by 50 authors in 450 pages of text, although the same 27 chapter headings are used. The chapter "Parenteral and Enteral Nutrition" has trebled, "Nutrition and Brain Development" has doubled. The book attempts to be a practical compilation of accepted information on nutrition in health and disease, without in any way constituting itself as a reference text or a source for background scientific information. Most chapters include a rationale for nutritional therapy or
TCT-588 Optical Coherence Tomography Guided Analysis of Coronary Artery Plaque Composition, Morphology and Burden and their Effect on ABSORB Bioresorbable Vascular Scaffold Expansion and Eccentricity.
Authors: Elizabeth Shaw, Usaid K. Allahwala, Thomas C. Hansen, James A. Cockburn, Peter S. Hansen, Gemma A. Figtree, Jawad Mazhar, Ravinay Bhindi
Journal: Journal of the American College of Cardiology (2013)
SHO training. Assessment initiative in accident and emergency.
Authors: K Reynard, J K Gosnold, P Grout
Journal: BMJ (1993)

15 '5 0 z I0 5 0 0 5 O I5 20 25 30 35 40 45 50 55 Vitamin K (mg/I)Plasma vitamin K concentrations at age 96-120 hours in 88 infants given I mg vitamin K intramuscularly and in 88 given 2 mg orally significant difference in the mean vitamin K con- centrations between the groups (t test), and the distributions of the concentrations were similar.None of these patients developed late haemor- rhagic disease of the newborn.These results suggest that a larger dose of vitamin K is needed for oral administration than for intramuscular administration to maintain similar plasma vitamin K concentrations at 97-120 hours.Follow up studies are needed to establish whether 2 mg vitamin K given orally at birth is as effective prophylaxis as 1 mg given intra- muscularly.
The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats
Authors: T. Sladek, J. Sladkova, F. Kolar, F. Papousek, N. Cicutti, B. Korecky, K. Rakusan
Journal: Cardiovascular Research (1996)

The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction.Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals.Infarcted hearts were characterized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)max, whereas left ventricular end-diastolic pressure (LVEDP), relaxation constant tau and right ventricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVSP in the infarcted hearts. Right ventricular weight significantly increased in rats with infarction; this was attenuated by losartan. Infarct size was not significantly influenced by losartan treatment. Morphometric data revealed decreased capillary supply in infarcted hearts, especially in regions close to infarction; the decrease was less pronounced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm2 to 1471/mm2 in untreated animals but in the treated animals it decreased from 2982/mm2 to only 2037/mm2. Simultaneous significant decrease in myocyte-to-capillary ratio in treated animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP was dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was found.Decreased ventricular contractility, prolonged relaxation and decreased coronary capillary density in rat experimental cardiac infarction confirm and amplify previous reports dealing with this experimental model. Moreover, we have found evidence of improved hemodynamics and coronary angiogenesis after losartan treatment.
Hepatic Drug Metabolism and Malignancy
Authors: Nicholas F. LaRusso
Journal: JAMA (1976)

Weighing between 1,400 and 1,600 gm in the adult, the liver is the largest internal organ in the human body. Its rich blood supply originates from two separate sources, the hepatic artery and the portal vein, the latter draining all the organs of the digestive tract. The liver exhibits a unique cellular architecture that permits blood to percolate through hepatic parenchyma, constantly exposing the hepatocyte to a variety of endogenous and exogenous substances. It also possesses the capacity to excrete certain of these substances into bile. Because of these characteristics, the human liver is both the major site of drug metabolism 1 and the most common location of distant metastases from a variety of malignant tumors.  The hepatocyte contains enzymes that oxidize and conjugate chemical substances, modifying their pharmacologic characteristics and increasing their excretability in bile and urine. These enzymes are located primarily in the smooth endoplasmic reticulum, an interconnecting
Reviews and Notes: Geriatrics: The Moral Challenge of Alzheimer Disease
Authors: Paula Bonino
Journal: Annals of Internal Medicine (1996)

Literature of Medicine1 October 1996Reviews and Notes: Geriatrics: The Moral Challenge of Alzheimer DiseasePaula Bonino, MDPaula Bonino, MDUniversity of Pittsburgh, Pittsburgh, PA 15213Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-7-199610010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail SG Post. 126 pages. Baltimore: Johns Hopkins Univ Pr; 1995. $29.95. ISBN 0801851742. Order phone 800-537-5487.Alzheimer disease is challenging from many perspectives, including the moral perspective. This book's alternate title is “Why Care?”, and its purpose is to help family members, health professionals, persons at risk, and students of ethics deal with the challenge of Alzheimer disease and the moral and ethical issues it creates.The text focuses first on global moral challenges and then on specific aspects of care. The author uses case examples to show the realities of Alzheimer disease. The first three chapters look at the ... Author, Article, and Disclosure InformationAffiliations: University of Pittsburgh, Pittsburgh, PA 15213 Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1996Volume 125, Issue 7Page: 624KeywordsAlzheimer diseaseDementiaEuthanasiaGeriatricsPatient advocacyPatientsQuality of lifeSuicideTreatment guidelines ePublished: 15 August 2000 Issue Published: 1 October 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.
Authors: J R Stratton, M D Cerqueira, R S Schwartz, W C Levy, R C Veith, S E Kahn, I B Abrass
Journal: Circulation (1992)

Cardiac aging is characterized by a reduced heart rate response to beta-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced beta-agonist responses can be improved with exercise training has not been determined in humans.Cardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60-82 years) and 17 young (age, 24-32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p less than 0.001), systolic blood pressure (+9% versus +24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p less than 0.05), ejection fraction (+12 versus +20 ejection fraction units, p less than 0.001), and cardiac output (+70% versus +100%, p less than 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128 +/- 58, 227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/- 20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups.We conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol in healthy men. Altered beta-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to beta-adrenergic stimulation with isoproterenol in either young or older men. The reduced beta-adrenergic response appears to be a primary age-associated change that is not caused by disease or inactivity.
The Prevention of Suicide
Authors: D Wasserman
Journal: BMJ (1994)

The Prevention of Suicide stems from a conference organised by the former Department of Health and Social Security, the Faculty of Public Health Medicine, the Royal College of General Practitioners, and the Royal College of Psychiatrists. It may be seen as an important step towards developing a comprehensive national strategy for preventing suicide and attempted suicide - a strategy advocated for all countries over the past decade by the World Health Organisation and since 1993 by the United Nations.

Suicide occurs in developing and industrialised countries alike, among all age groups and social classes. Every year at least 500 000 people throughout …
Using the BTS CAP audit to evaluate local data
Authors: B Singh, D G Wootton, J Brown, B Chakrabarti, R P D Cooke, S B Gordon
Journal: Thorax (2011)

We read Dr Lim and Dr Woodhead's update on the British Thoracic Society (BTS) 2009/2010 community acquired pneumonia (CAP) audit with interest and noted the high inpatient mortality rate of 18.3%.1 As a contributing site, we received a useful summary of our data in comparison with the national data and local mortality rates for severe CAP (CURB65 3-5) were 21.4% versus 42.6% nationally. This provoked an examination of local severe CAP admissions between December 2009 and …
Antipsychotic Agents and Sudden Cardiac Death — How Should We Manage the Risk?
Authors: Sebastian Schneeweiss, Jerry Avorn
Journal: New England Journal of Medicine (2009)

Antipsychotic medications are commonly used across the entire age spectrum, both within and outside their labeled (and evidence-based) indications.1,2 Three atypical antipsychotic medications, olanzapine (Zyprexa, Eli Lilly), risperidone (Risperdal, Janssen), and quetiapine (Seroquel, AstraZeneca) are among the 10 top-selling drugs worldwide, with a combined sales volume of $14.5 billion in 2007.3 A thorough evaluation of risks is particularly important in the case of medications that are used so frequently and in such diverse patients, many of whom (e.g., children and the elderly) are particularly vulnerable. The effect of most antipsychotic medications on the electrophysiology of the heart has long . . .
Children have been neglected in flu prevention strategy
Authors: O. Dyer
Journal: BMJ (2003)

The northern hemisphere is bracing itself for a severe influenza season this winter, with reported deaths in Europe and North America surpassing the early seasonal figures from recent years and a new strain of the virus circulating in the population.

Type A Fujian flu made headlines in Australia during that country's winter, when about 3000 people succumbed to flu and its complications. In Britain, two English and three Scottish children died from the Fujian flu in November. That is considered a high toll so early in the season.

France, Spain, Norway, and Portugal are reporting high infection rates among children. The southwestern United States has also seen an early onset, with vaccine demand outstripping production. “People wishing to be vaccinated may need to be persistent to …
Funding for GP out of hours in England has fallen by 65m since 2012
Authors: G. Iacobucci
Journal: BMJ (2014)

Funding for out of hours general practitioner services in England has decreased by some 13% in the past two years, new figures have shown.

Urgent Health UK, the representative body for GP social enterprise providers, said that the squeeze on finances made it “impossible” for some areas to provide a high quality service and placed more pressure on already overstretched emergency departments.

As of April 2014 the organisation estimated that the value of out of hours GP contracts across England stood at £435m (€530m; $731m)—down from around £500m when the organisation last surveyed healthcare commissioners in April 2012.

The research, seen by The BMJ but not publicly available, was conducted by Urgent Health UK as part of a market analysis. It was based on …
Selectin and selectin ligand binding: a bittersweet attraction
Authors: Thomas M. Zollner, Khusru Asadullah
Journal: Journal of Clinical Investigation (2003)

Inhibition of leukocyte migration into target organs has long been an attractive, though challenging, basis for anti-inflammatory strategies. However, to date, the manipulation of leukocyte rolling along blood vessels has not yielded successful new therapies. An important study may now open new avenues in this exciting field of anti-inflammatory therapies by introducing a putative inhibitor of poly-N-acetyllactosamine biosynthesis that affects selectin ligand activity and shows efficacy in a rodent skin inflammation model.
Safer Administration of Intravenous Anaesthetics
Authors: D. C. Clark
Journal: BMJ (1947)

Many Russians in my care during the war, even those who had been wounded before capture, awaited their return home with extreme terror.Why ?I agree that social security, whatever it may mean, has tended to reduce effort for the reasons advanced by Dr. Crichton-Miller.Many economists suggest that the economic basis for this social security is crumbling, so we may soon see the next phase developing.-Iam, etc.,
Mortality among Living Kidney Donors and Comparison Populations
Authors: Julie Lin, Holly Kramer, Anil K. Chandraker
Journal: New England Journal of Medicine (2010)

which to omit.We agree with Maslove and Mihm that needle guides can be helpful; however, needle guides are not universally available.Augoustides et al., the authors of the article they cite, conclude that needle guides are most helpful in improving the performance of the the novice operator and that the difference made when a guide is used disappears with experience.In addition, the use of a needle guide offers no protection against arterial puncture. 1Movahed suggests that micropuncture should be the standard of care.He bases this recommendation on a report by Blaivas and Adhikari in which mannequins were used and in which the hypothesis concerning the benefit of micropuncture for ultrasound-guided central venous catheterization was not tested. 2 Clinicians performing any medical procedure modify the technique used on the basis of their experience, preferences, and information obtained from scientific publications.Our video was designed to be a starting point for this process.