tbuckley/cabot-search huggingface dataset:
Release of Adenosine from Ischemic Brain
Authors: ROBERT M. BERNE, RAFAEL RUBIO, RICHARD R. CURNISH
Journal: Circulation Research (1974)

A threefold increase in tissue adenosine levels was produced by ischemia in the dog and the rat brain within 1 minute; adenosine levels increased further with longer periods of ischemia. Inosine and hypoxanthine were also increased by ischemia but to different degrees. The nucleosides and hypoxanthine appeared in cerebrospinal fluid during ischemia in the dog brain, and incubation of adenosine in normal cerebrospinal fluid failed to show the presence of degradative enzymes. Intra-arterially administered adenosine in the dog and the cat produced little or no increase in cerebral blood flow or the diameter of pial arterioles, respectively, when it was given in amounts that reduced arterial blood pressure. However, when it was applied topically to exposed pial arterioles of the cat, adenosine induced dilation that was roughly proportional to the dose used. When U- 14 C-adenosine was infused into the internal carotid arteries of the dog, no radioactivity was detectable in the cerebrospinal fluid and practically none appeared in the brain tissue. When labeled adenosine was added to dog cerebrospinal fluid, only a few counts appeared in the cerebral venous blood, whereas cerebral tissue was heavily labeled with 84-87% of the radioactivity in the form of adenine nucleotides. In the rat, after intravenous injection of labeled adenosine, the counts per gram of heart were twenty- to thirtyfold greater than those per gram of brain. These observations indicate that intra-arterially administered adenosine probably fails to cross the blood-brain barrier rapidly enough to influence cerebral blood flow but that it can be released from the ischemic brain into the cerebrospinal fluid and be reincorporated from the cerebrospinal fluid into brain nucleotides. Hence, adenosine can conceivably participate in the regulation of cerebral blood flow.
Renal cortical blood flow in glycerol-induced acute renal failure in the rat.
Authors: T W Kurtz, R M Maletz, C H Hsu
Journal: Circulation Research (1976)

Renal hemodynamics and renal function were evaluated in rats at 3, 24, and 48 hours and at 7 days after the induction of acute renal failure (ARF) by glycerol injection. Three hours after induction of ARF, creatinine clearance was 0.04 ml/min/100 g; renal blood flow (RBF), 1.99 ml/min/100 g; and filtration fraction, 3.7%. All were abnormally low. Although the administration of isotonic saline (total dose, 3% of body weight) to rats 3 hours after glycerol injection significantly improved creatinine clearance (0.17 ml/min/100 g), RBF (2.54 ml/min/100 g), and filtration fraction (12.9%), these values still were significantly lower than those of controls (creatinine clearance = 0.50 ml. ml/min/100 g, RBF = 4.92 ml/min/100 g, filtration fraction = 20.0%, all P values less than 0.001). Serum creatinine concentrations were significantly elevated at 24 hours (3.72% gm/100 ml), 48 hours (4.69 mg/100 ml), and 7 days (0.66 mg/100 ml) after glycerol injection compared to control (0.46 mg/100 ml, all P less than 0.01). RBF during these phases was not different from normal (4.41 ml/min/100 g). RBF 3 hours after bilateral ureteral obstruction was measured to determine the effects of tubular obstruction on renal hemodynamics. The RBF of rats with ureteral obstruction (4.12 ml/min/100 g) was not significantly different from controls (4.41 ml/min/100 g), suggesting that tubular obstruction in this model of ARF is probably not the cause of decreased RBF. The depressed glomerular filtration, as reflected by the decreased creatinine clearance that occurs during glycerol-induced ARF, is probably related to altered intrarenal vascular resistance or to changes in glomerular capillary permeability, or both.
Pregnancy induces minor histocompatibility antigen–specific cytotoxic T cells: implications for stem cell transplantation and immunotherapy
Authors: Rob M. Verdijk, Antoinette Kloosterman, Jos Pool, Maarten van de Keur, Albert M. I. H. Naipal, Astrid G. S. van Halteren, Anneke Brand, Tuna Mutis, Els Goulmy
Journal: Blood (2003)
336 INTERFERON LAMBDA-PRODUCING CD141+ DENDRITIC CELLS ARE ENRICHED IN HEALTHY HUMAN LIVER AND PRIME INTERFERON-GAMMA AND IL-17-SECRETING T CELLS
Authors: A. Kelly, R. Fahey, J.M. Fletcher, C. Keogh, A.G. Carroll, R. Siddachari, J. Geoghegan, J.E. Hegarty, E.J. Ryan, C. O'Farrelly
Journal: Journal of Hepatology (2013)
Experts express doubts that food and drink industries have the motives to improve health
Authors: A. O'Dowd
Journal: BMJ (2011)

<h3>Objectives</h3> The Shape of Training report recommended that full registration is aligned with medical school graduation. As part of a General Medical Council-funded study about the preparedness for practice of UK medical graduates, we explored UK stakeholders’ views about this proposal using qualitative interviews (30 group and 87 individual interviews) and Framework Analysis. <h3>Setting</h3> Four UK study sites, one in each country. <h3>Participants</h3> 185 individuals from eight stakeholder groups: (1) foundation year 1 (F1) doctors (n=34); (2) fully registered trainee doctors (n=33); (3) clinical educators (n=32); (4) undergraduate/postgraduate Deans, and Foundation Programme Directors (n=30); (5) other healthcare professionals (n=13); (6) employers (n=7); (7) policy and government (n=11); (8) patient and public representatives (n=25). <h3>Results</h3> We identified four main themes: (1) <i>The F1 year as a safety net</i>: patients were protected by close trainee supervision and ‘sign off’ to prevent errors; trainees were provided with a safe environment for learning on the job; (2) <i>Implications for undergraduate medical education</i>: if the proposal was accepted, a ‘radical review’ of undergraduate curricula would be needed; undergraduate education might need to be longer; (3) <i>Implications for F1 work practice</i>: steps to protect healthcare team integration and ensure that F1 doctors stay within competency limits would be required; (4) <i>Financial, structural and political implications:</i> there would be cost implications for trainees; clarification of responsibilities between undergraduate and postgraduate medical education would be needed. Typically, each theme comprised arguments for and against the proposal. <h3>Conclusions</h3> A policy change to align the timing of full registration with graduation would require considerable planning and preliminary work. These findings will inform policymakers’ decision-making. Regardless of the decision, medical students should take on greater responsibility for patient care as undergraduates, assessment methods in clinical practice and professionalism domains need development, and good practice in postgraduate supervision and support must be shared.
Determining the Ideal Strategy for Ventilator-associated Pneumonia Prevention. Cost–Benefit Analysis
Authors: Westyn Branch-Elliman, Sharon B. Wright, Michael D. Howell
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection with high associated cost and poor patient outcomes. Many strategies for VAP reduction have been evaluated. However, the combination of strategies with the optimal cost-benefit ratio remains unknown.To determine the preferred VAP prevention strategy, both from the hospital and societal perspectives.A cost-benefit decision model with a Markov model was constructed. Baseline probability of VAP, death, reintubation, and discharge from the intensive care unit (ICU) alive were ascertained from clinical trial data. Model inputs were obtained from the medical literature and the U.S. Department of Labor; a device cost was obtained from the manufacturer. Sensitivity analyses were completed to test the robustness of model results.Overall least expensive strategy and the strategy with the best cost-benefit ratio, up to a willingness to pay threshold of $50,000-100,000 per case of VAP averted was sought. We examined a total of 120 unique combinations of VAP prevention strategies. The preferred strategy from the hospital perspective included subglottic suction endotracheal tubes, probiotics, and the Institute for Healthcare Improvement VAP Prevention Bundle. The preferred strategy from the point of view of society also included additional prevention measures (oral care with chlorhexidine and selective oral decontamination). No preferred strategies included silver endotracheal tubes or selective gut decontamination.Despite their infrequent use, current data suggest that the use of prophylactic probiotics and subglottic endotracheal tubes are cost-effective for preventing VAP from the societal and hospital perspectives.
Neurotrophic and Neuroprotective Actions of Estrogens and Their Therapeutic Implications
Authors: Susan J Lee, Bruce S McEwen
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Originally known for its regulation of reproductive functions, estradiol, a lipophilic hormone that can easily cross plasma membranes as well as the blood-brain barrier, maintains brain systems subserving arousal, attention, mood, and cognition. In addition, both synthetic and natural estrogens exert neurotrophic and neuroprotective effects. There is increasing evidence that estrogen actions are mediated by nongenomic as well as direct and indirect genomic pathways. Although in vitro models have provided the most extensive evidence for neurotrophic and neuroprotective actions to date, there are also in vivo studies that support these actions.
Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria
Authors: Robert A. Brodsky, Neal S. Young, Elisabetta Antonioli, Antonio M. Risitano, Hubert Schrezenmeier, Jörg Schubert, Anna Gaya, Luke Coyle, Carlos de Castro, Chieh-Lin Fu, Jaroslaw P. Maciejewski, Monica Bessler, Henk-André Kroon, Russell P. Rother, Peter Hillmen
Journal: Blood (2007)
TCT-267 Comparison of Coronary Plaque Components between Non-Culprit Lesion in Patients with Acute Coronary Syndrome and Target Lesion in Patients with Stable Angina: Virtual Histology-Intravascular Ultrasound Analysis
Authors: Young Joon Hong, Myung Ho Jeong, Yun Ha Choi, Soo Young Park, Jae Yeong Cho, Hae Chang Jeong, Sang Cheol Cho, Su Young Jang, Ji Eun Song, Jong Hyun Yoo, Doo Sun Sim, Keun Ho Park, Ju Han Kim, Youngkeun Ahn, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2012)
43 ADIPOSE TRIGLYCERIDE LIPASE (ATGL) IS A NOVEL KEY PLAYER IN PROTECTION FROM ACUTE HEPATIC INFLAMMATION
Authors: P. Kumari, T. Claudel, H. Köfeler, M. Schittmayer, R.B. Grünberger, R. Zechner, G. Höfler, M. Trauner
Journal: Journal of Hepatology (2010)
Serological data improves estimates of infection during 2009 H1N1 pandemic
Authors: H. K. Bayes
Journal: Thorax (2010)

The 2009 global pandemic of swine origin influenza A H1N1 virus resulted in substantial public health and vaccination efforts. This cross-sectional serological survey from the UK Health Protection Agency estimated the level of pre-existing immunity to the virus and the incidence of infection in the population during the first wave of H1N1 in England.

Pre-pandemic serum …
<i>Gata2</i> cis-element is required for hematopoietic stem cell generation in the mammalian embryo
Authors: Xin Gao, Kirby D. Johnson, Yuan-I Chang, Meghan E. Boyer, Colin N. Dewey, Jing Zhang, Emery H. Bresnick
Journal: The Journal of Experimental Medicine (2013)

The generation of hematopoietic stem cells (HSCs) from hemogenic endothelium within the aorta, gonad, mesonephros (AGM) region of the mammalian embryo is crucial for development of the adult hematopoietic system. We described a deletion of a Gata2 cis-element (+9.5) that depletes fetal liver HSCs, is lethal at E13-14 of embryogenesis, and is mutated in an immunodeficiency that progresses to myelodysplasia/leukemia. Here, we demonstrate that the +9.5 element enhances Gata2 expression and is required to generate long-term repopulating HSCs in the AGM. Deletion of the +9.5 element abrogated the capacity of hemogenic endothelium to generate HSC-containing clusters in the aorta. Genomic analyses indicated that the +9.5 element regulated a rich ensemble of genes that control hemogenic endothelium and HSCs, as well as genes not implicated in hematopoiesis. These results reveal a mechanism that controls stem cell emergence from hemogenic endothelium to establish the adult hematopoietic system.
Severe hepatotoxic reaction with progression to cirrhosis after use of a novel retinoid (acitretin)
Authors: Th.J.M. van Ditzhuijsen, U.J.G.M. van Haelst, R.J. van Dooren-Greebe, P.C.M. van de Kerkhof, S.H. Yap
Journal: Journal of Hepatology (1990)
Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients
Authors: Megumu Saito, Ryuta Nishikomori, Naotomo Kambe, Akihiro Fujisawa, Hideaki Tanizaki, Kyoko Takeichi, Tomoyuki Imagawa, Tomoko Iehara, Hidetoshi Takada, Tadashi Matsubayashi, Hiroshi Tanaka, Hisashi Kawashima, Kiyoshi Kawakami, Shinji Kagami, Ikuo Okafuji, Takakazu Yoshioka, Souichi Adachi, Toshio Heike, Yoshiki Miyachi, Tatsutoshi Nakahata
Journal: Blood (2007)
Biological agents for ulcerative colitis: Hypes and hopes
Authors: Silvio Danese, Erika Angelucci, Alberto Malesci, Renzo Caprilli
Journal: Medicinal Research Reviews (2007)

Abstract Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colonic mucosa. Over the last decade, the increasing knowledge on the pathogenic mechanisms underlying intestinal inflammation has led to the development of a number of biological agents, mainly addressed to molecules and/or pathways demonstrated to have a pathogenic role in UC. In UC, clinical course and therapeutic decisions mainly depend on disease activity and extent. While therapeutic approach to mild‐to‐moderate UC by using aminosalicylates and corticosteroids has been well established, treatment of severe UC is far from being satisfactory. A severe attack of UC remains a challenge to be managed jointly by gastroenterology, surgery, and intensive care units. However, the recent introduction of biological therapies has led to promising changes in the management of UC patients. Aim of this paper is to review the recent advances and future perspectives for the use of biological agents in UC. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 201–218, 2008
Paediatric non-alcoholic fatty liver disease
Authors: V. Nobili, M. Pinzani
Journal: Gut (2010)

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from asymptomatic steatosis, with or without elevated aminotransferases, to cirrhosis with relative complications and hepatocellular carcinoma.1 The histological appearance ranges from simple steatosis to hepatocellular damage coupled with inflammation (ie, non-alcoholic steatohepatitis (NASH)) and/or fibrosis.2 The emergence of NAFLD and NASH as clinically relevant entities has parallelled the increasing attention on the metabolic syndrome associated or not with obesity and the central role of insulin resistance, known for a long time to be related to chronic liver disease. However, clinicopathological studies in patients with NASH, as well as recent treatment trials with insulin-sensitising agents, have confirmed that insulin resistance is a cause, not a result, of liver disease.3–6

Paediatric NAFLD has become the most frequent chronic liver disease in children and adolescents in industrialised countries due to the growing prevalence of childhood obesity and overweight (figure 1).7 9 NAFLD affects from 2.6% to 9.8% of children and adolescents, and this figure increases up to 74% among obese individuals.9–12 The disease is also significantly associated with type 2 diabetes mellitus and all features of the metabolic syndrome (MetS).8 12 13 A recent survey on adolescent participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2004 found elevated alanine aminotransferase (ALT) in 8% of US adolescents aged 12–19 years. However, this survey is based only on the abnormality of ALT values and, since ALT is not a precise indicator for the presence of NAFLD, the true prevalence could be significantly higher.14 In a case series of autopsies performed on children 2–19 years of age at the time of death, the prevalence of histologically proven NAFLD was 9.6%.1 A more precise estimate of the prevalence of NAFLD and NASH can be obtained by evaluating obese …
Design of Retroviral Vectors and Helper Cells for Gene Therapy
Authors: Wei-Shau Hu, Vinay K. Pathak
Journal: Pharmacological Reviews (2000)

During the past decade, gene therapy has been applied to the treatment of disease in hundreds of clinical trials. Various tools have been developed to deliver genes into human cells; among them, genetically engineered retroviruses are currently the most popular tool for gene delivery. Most of the systems contain vectors that are capable of accommodating genes of interest and helper cells that can provide the viral structural proteins and enzymes to allow for the generation of vector-containing infectious viral particles. Retroviridae is a family of retroviruses that differs in nucleotide and amino acid sequence, genome structure, pathogenicity, and host range. This diversity provides opportunities to use viruses with different biological characteristics to develop different therapeutic applications. Currently, a variety of retroviruses that provide distinct advantages for gene delivery has been modified and used in clinical trials. In this review, the genome structures of oncoviruses, lentiviruses, and spumaviruses are reviewed and examples of vectors derived from these viruses are described. As with any delivery tool, the efficiency, the ability to target certain tissue or cell type, the expression of the gene of interest, and the safety of retroviral-based systems are important for successful application of gene therapy. Significant efforts have been dedicated to these areas of research in recent years. Various modifications have been made to retroviral-based vectors and helper cells to alter gene expression, target delivery, improve viral titers, and increase safety. The principles and design of these modifications are discussed in this review.
Arthropathy of Wilson's disease. Study of clinical and radiological features in 32 patients.
Authors: D N Golding, J M Walshe
Journal: Annals of the Rheumatic Diseases (1977)

The principal clinical features and radiological findings relating to the locomotor system have been studied in 32 consecutive hospital admissions of patients with Wilson9s disease. 5 of these patients were recently diagnosed and had as yet received no treatment, while 27 were routine admissions for follow-up and biochemical supervision of their illness. No patient was specifically included or excluded from the series because of the presence or absence of locomotor symptoms. The most common radiological abnormality was a generalized increase of radiolucency, interpreted as skeletal demineralization (21 cases), followed by premature osteoarthrosis (8 cases). Changes in the spine were common and included osteochondritis, reduction of intervertebral joint spaces, osteoarthrosis, and a tendency to squaring of vertebral bodies. Other bony changes included fluffy irregularity of femoral trochanters, osteochondritis dissecans of the knees, osteophytic protrusions at bone ends, and bunches of tongue-like osteophytes at joint margins. The symptoms associated with these radiological abnormalities comprised back pain and stiffness with restricted movement, pain and stiffness of knees, hips, and wrists, and tenderness to pressure over margins of affected joints. Joint hypermobility was also observed in 9 patients. Episodes of acute polyarthritis with serological changes were seen in 5 cases; all these episodes appeared to be related directly to treatment with penicillamine.
A Geometrical Model of Successive Stages in Excitation of the Human Heart; its Value as a Link between Excitation and Clinical Vectorcardiography
Authors: A. C. Arntzenius
Journal: Cardiovascular Research (1969)

Journal Article A Geometrical Model of Successive Stages in Excitation of the Human Heart; its Value as a Link between Excitation and Clinical Vectorcardiography Get access A. C. Arntzenius A. C. Arntzenius From the Department of Cardiology, University Hospital, Leiden, the Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 2, April 1969, Pages 198–208, https://doi.org/10.1093/cvr/3.2.198 Published: 01 April 1969 Article history Received: 02 August 1968 Published: 01 April 1969
Electronic Medical Records: Saving Trees, Saving Lives
Authors: Dena E. Rifkin
Journal: JAMA (2001)

CONSIDER THIS IRONY OF MODERN LIFE: IN A MEDICAL CRISIS, EMERGENCY physicians would have an easier time accessing a patient’s bank account using his or her automatic teller machine card than they would finding critical medical history using his or her medical insurance card. Medical records, including crucial electrocardiograms, drug allergies, or medical conditions, are typically stored on paper and are often inaccessible in emergencies. The ability to access medical charts electronically, in emergency situations or in routine medical settings, has not paralleled the growth of financial networks or indeed of the Internet. Although several commercial sites are now selling space for individuals to put their medical records online and numerous institutions have local electronic medical records (EMRs) in place, most clinical records are still kept in paper charts that are stored at a single location. The challenge of building an integrated EMR system has proved to be more than technological; 25 years of attempts to formalize the terms and concepts of medical practice has exposed some fascinating philosophical conundrums. What belongs in a medical record, and how should medical conditions or ideas be encoded? Which tasks are best performed by physicians, and which by the computer? Is it possible to encapsulate the medical encounter in digital form? A number of centers have had local EMRs available for decades, providing evidence that thoughtfully implemented EMRs improve medical care through adjunct technology like error checking and allow easier study of trends in a clinic population. New links are being forged between individual patient data and the information in digital libraries or the tools of computerized decision support. While the potential for ease of access and error reduction seems obvious, new technologies should be held to the same standards of evidence as new treatments are. Research in this field has started to look not only at efficiency and institutional satisfaction but also at health outcomes and impact on the patient-physician relationship. As researchers measure the gains made by using EMRs, they should also consider potential losses. Will physicians rely too heavily on the safety nets of automatic warning systems, losing the ability to think through the problem—just as many who rely on calculators cannot compute answers on their own? With full histories available at the touch of a button, will tired interns and residents cut corners, neglecting to ask their own questions? EMRs must be a tool for improving patient care rather than a crutch or a hindrance to the primary work of caring for patients. This month, MSJAMA examines the legal, ethical, and technical challenges of EMRs. With a new generation of physicians accustomed to working with computer technology, we may see some of the promise of the past 3 decades of research in this field come to fruition in the coming years.