tbuckley/cabot-search huggingface dataset:
Getting the balance right
Authors: D M H Smith
Journal: BMJ (1986)

<h3>Background</h3> Patent foramen ovale (PFO) is a common form of atrial septal defect where there is incomplete closure of the septum secundum, leaving a small residual opening. Very large ones can be detected in 25% of autopsies, while small defects (0.5-1.0 cm) are present in about 6%. Most patients with PFOs are asymptomatic; however in conditions giving rise to high right-sided pressures there may be right to left shunt across the PFO, which can be easily missed unless one has a high index of suspicion for it. <h3>Case Report</h3> A 65-year-old white woman was transferred from surgical services to coronary care unit (CCU) following an ST-elevation inferior wall and right ventricular myocardial infarction with hypotension and respiratory failure. The patient received thrombolysis and improved over the next few days. However, even though all parameters pointed toward an upward trend in terms of improvement, it was difficult to wean the patient off the ventilator. She continued to require increasing oxygen concentration to maintain her saturation, and even at a FiO<sub>2</sub> of 80%, her saturations were only in the range of 88-90%. She had no evidence of pulmonary embolism, pneumonia, or any other apparent causes that could have explained her large A-a gradient. At that point echocardiography was done with agitated saline bubble contrast, which demonstrated a large PFO, giving rise to a large right to left shunt. That explained her desaturation and her intolerance to weaning. No aggressive measures were taken at that time, but in the next 2 days, as the patient came out of failure, it was possible to take her off the ventilator. <h3>Teaching Point</h3> It is important to remember that in the setting of right ventricular failure, it is prudent to keep in mind the possibility of an undiagnosed PFO any time we are trying to explain hypoxia or desaturation. Diagnosis can be made with simple bedside echocardiogram with saline bubble contrast study. It might also save extensive work-up for other causes of hypoxia in this setting.
Résection endoscopique par mucosectomie des polypes recto-coliques de plus de deux centimètres
Authors: H Mounier-Boutoille, D O'Toole, MC Rousselet, P Burtin, D Luet, J Boyer
Journal: Endoscopy (2008)

Rationnel: La mucosectomie endoscopique est efficace pour des lésions <2cm – une résection en monobloc est possible permettant une analyse histologique complète. La résection des lésions >2cm est possible par la technique de fragmentation ou la dissection de la sous muqueuse (ESD). La technique par fragmentation reste controversée car elle expose aux risques de laisser en place des fragments pathologiques et l'analyse histologique des marges latérales des pièces/fragments est non interprétable.
Pagophagia and Iron Lack
Authors: Charles A. Coltman
Journal: JAMA (1969)

Iron lack was associated with an unusual perversion of appetite characterized by the ingestion of extraordinary amounts of ice. Pagophagia is defined as the purposeful ingestion of at least one ordinary tray of ice daily for a period in excess of two months. The symptom appears to be related to iron lack and is completely resolved with amounts of iron less than those required for resolution of the anemia or replenishment of iron stores. The data on the rates of repair of mucosal cytochrome and blood-cell hemoglobin coincide with the temporal relationship between the resolution of pagophagia and the correction of iron-lack anemia.
FDA Regulation of Prescription Drug Advertising
Authors: Carl C. Peck
Journal: JAMA (1990)

Dr Kessler and Mr Pines<sup>1</sup>present a thoughtful and balanced review of the Food and Drug Administration's (FDA) regulation of prescription drug promotion. In their conclusion, the authors call to mind issues where the need for change is clear and other issues that have long vexed the agency. Mr Pines, a former FDA Associate Commissioner for Public Affairs, is intimately familiar with these issues and has chaired conferences on them in several forums. Many of the presentations from these conferences have been published.<sup>2,3</sup> The article makes some cogent observations. The need to revise the brief summary for use in advertising in a way that makes it readable and more useful is inescapable. The need for governmental oversight of promotional activities involving gifts and other financial inducements to health care providers, such as travel, was made clear in hearings conducted by Sen Edward Kennedy of Massachusetts as early as
Sarcoid lesion in breast after probable sarcoidosis in lung.
Authors: B Rigden
Journal: BMJ (1978)

salicylic acid (1-8-3 6 g/day) in hospital (figure).The two other patients had taken acetylsalicylic acid before admission and had raised serum AST concentrations, which were subsequently normal.Serum AST concentrations were affected in all, and gamma-glutamyltransferase and glutamic purpuric transaminase concentrations were also affected in four patients.All other liver function tests were normal.No patient was taking other drugs (including alcohol) known to influence liver function tests, and all had negative tests for hepatitis B antigen.
The Minimal Active Domain of Endostatin Is a Heparin-Binding Motif that Mediates Inhibition of Tumor Vascularization
Authors: Anna-Karin Olsson, Irja Johansson, Helena Åkerud, Barbro Einarsson, Rolf Christofferson, Takako Sasaki, Rupert Timpl, Lena Claesson-Welsh
Journal: Cancer Research (2004)

Abstract Endostatin constitutes the COOH-terminal 20,000 Da proteolytic fragment of collagen XVIII and has been shown to possess antiangiogenic and antitumorigenic properties. In the present study, we have investigated the role of the heparin-binding sites in the in vivo mechanism of action of endostatin. The majority of the heparin binding is mediated by arginines 155/158/184/270 in endostatin, but there is also a minor site constituted by arginines 193/194. Using endostatin mutants lacking either of these two sites, we show that inhibition of fibroblast growth factor-2–induced angiogenesis in the chicken chorioallantoic membrane requires both heparin-binding sites. In contrast, inhibition of vascular endothelial growth factor-A–induced chorioallantoic membrane angiogenesis by endostatin was only dependent on the minor heparin-binding site (R193/194). These arginines were also required for endostatin to inhibit fibroblast growth factor-2– and vascular endothelial growth factor-A–induced chemotaxis of primary endothelial cells. Moreover, we show that a synthetic peptide corresponding to amino acids 180–199 of human endostatin (which covers the minor heparin-binding site) inhibits endothelial cell chemotaxis and reduces tumor vascularization in vivo. Substitution of arginine residues 193/194 for alanine attenuates the antiangiogenic effects of the peptide. These data show an essential role for heparin binding in the antiangiogenic action of endostatin.
RNA-seq analysis of 2 closely related leukemia clones that differ in their self-renewal capacity
Authors: Brian T. Wilhelm, Mathieu Briau, Pamela Austin, Amélie Faubert, Geneviève Boucher, Pierre Chagnon, Kristin Hope, Simon Girard, Nadine Mayotte, Josette-Renee Landry, Josée Hébert, Guy Sauvageau
Journal: Blood (2010)
Aneurysm prevention: keep the cat out of the bag
Authors: K. J. Rodgers, C. L. Jackson
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Deficiency of cathepsin S attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice’ by Y. Qin et al ., pp. 401–410, this issue. 

In this issue of Cardiovascular Research , Qin et al. 1 show that the incidence of abdominal aortic aneurysm formation in apolipoprotein E (apo E) knockout mice is profoundly inhibited if the mice are additionally deficient in cathepsin S, an elastinolytic cysteine proteinase.

Cathepsin S, traditionally thought of as a lysosomal proteinase involved only in the terminal degradation of endocytosed proteins, is now known to be active in the cytosol, the nucleus, and the extracellular matrix and to play a number of diverse cell-specific roles, including the destruction of extracellular matrix collagen and elastin and weakening of the arterial wall.2,3 Some cells can also release cathepsin S in a regulated manner to facilitate their migration and, in the case of endothelial cells, to allow new blood vessels to invade tissue. An elegant study by Abdul-Hussien et al. 4 identified cathepsin S as the most highly up-regulated proteinase in abdominal aortic aneurysms: cathepsin K was up-regulated to a much lesser extent and its deletion was subsequently shown to have no effect on aneurysm development in mice.5 Cathepsin S is therefore an obvious therapeutic target, and, as Qin et al. have demonstrated, its removal is …
Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow
Authors: Jonathan J. Miner, Lijun Xia, Tadayuki Yago, János Kappelmayer, Zhenghui Liu, Arkadiusz G. Klopocki, Bojing Shao, J. Michael McDaniel, Hendra Setiadi, David W. Schmidtke, Rodger P. McEver
Journal: Blood (2008)
Relationship between placental blood flow and combined ventricular output with gestational age in normal human fetus
Authors: M. G S. J. Sutton, T. Plappert, P Doubilet
Journal: Cardiovascular Research (1991)

The aim was to quantify the changes in placental blood flow and combined ventricular output with gestational age in normal human fetuses to determine the percentage of total cardiac output that placental blood flow represented, and whether this changed with age.Two dimensional echocardiographic images of the umbilical vein, the proximal aorta and proximal main pulmonary artery were obtained, and cross sectional areas calculated from vessel diameters. Doppler velocity signals were recorded from each vessel and digitised to obtain velocity-time integrals. Placental blood volume flow and combined ventricular output were calculated as the products of flow velocity time integrals and cross sectional areas of the umbilical vein, and of the great arteries respective.Subjects were 64 normal human fetuses aged between 20 and 42 weeks gestation.Placental flow and combined ventricular output both increased exponentially with gestational age (r = 0.79, and r = 0.84; both p less than 0.001). Placental flow correlated linearly with combined ventricular output (r = 0.69; p less than 0.01) and comprised almost one third of total cardiac output throughout the second and third trimesters.These data describe the relationship between placental blood flow and combined ventricular output with age in the normal human fetus and provide a substrate by which placental insufficiency and resulting intrauterine growth retardation may be recognised early.
Pre-existing Immunity and Passive Immunity to Adenovirus 5 Prevents Toxicity Caused by an Oncolytic Adenovirus Vector in the Syrian Hamster Model
Authors: Debanjan Dhar, Jacqueline F Spencer, Karoly Toth, William SM Wold
Journal: Molecular Therapy (2009)

We have used Syrian hamsters to examine the role of pre-existing immunity to adenovirus (Ad) 5 in the toxicity of the oncolytic Ad vector INGN 007. Groups of hamsters were or were not immunized with Ad5. Half the hamsters were immunosuppressed using cyclophosphamide (CP), then injected intravenously (i.v.) with 3× the maximum tolerated dose (MTD) of INGN 007 (in immunocompetent hamsters), and toxicity and vector replication in the liver were quantitated. In nonimmunized immunocompetent hamsters, toxicity was observed early but the hamsters recovered by day 6 after vector injection. In nonimmunized immunosuppressed hamsters, the vector was lethal by 3 days. Pre-existing neutralizing antibody (NAb) prevented liver infection and hepatotoxicity in both immunocompetent and immunosuppressed hamsters. In another study, passive immunization of immunosuppressed hamsters 1 day before a lethal dose (1× MTD) of INGN 007 prevented liver infection and replication, but immunization 1 day after vector administration was barely effective. When immunosuppressed hamsters were passively immunized 1 day after injection of 1/3rd the MTD of INGN 007, then significant protection was observed against liver infection and toxicity. Therefore, serum NAb are sufficient to prevent oncolytic Ad vector liver infection and toxicity. We saw no evidence that pre-existing immunity was associated with increased vector toxicity. We have used Syrian hamsters to examine the role of pre-existing immunity to adenovirus (Ad) 5 in the toxicity of the oncolytic Ad vector INGN 007. Groups of hamsters were or were not immunized with Ad5. Half the hamsters were immunosuppressed using cyclophosphamide (CP), then injected intravenously (i.v.) with 3× the maximum tolerated dose (MTD) of INGN 007 (in immunocompetent hamsters), and toxicity and vector replication in the liver were quantitated. In nonimmunized immunocompetent hamsters, toxicity was observed early but the hamsters recovered by day 6 after vector injection. In nonimmunized immunosuppressed hamsters, the vector was lethal by 3 days. Pre-existing neutralizing antibody (NAb) prevented liver infection and hepatotoxicity in both immunocompetent and immunosuppressed hamsters. In another study, passive immunization of immunosuppressed hamsters 1 day before a lethal dose (1× MTD) of INGN 007 prevented liver infection and replication, but immunization 1 day after vector administration was barely effective. When immunosuppressed hamsters were passively immunized 1 day after injection of 1/3rd the MTD of INGN 007, then significant protection was observed against liver infection and toxicity. Therefore, serum NAb are sufficient to prevent oncolytic Ad vector liver infection and toxicity. We saw no evidence that pre-existing immunity was associated with increased vector toxicity.
Intra-articular thiotepa in rheumatoid arthritis.
Authors: H L Currey
Journal: Annals of the Rheumatic Diseases (1965)

Aims: The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells. Materials and Methods: In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IκB-α and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage). Results: Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction. Conclusion: It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.
Acral Changes Associated With Thyroid Diseases
Authors: Daniel W. Nixon
Journal: JAMA (1970)

Acral changes associated with thyroid diseases include exophthalmos, local myxedema, and acropachy, which may conveniently be grouped together for pathological and clinical reasons. This communication discusses 16 patients with acral changes following antithyroid therapy, and 8 patients who had not been hyperthyroid or received any form of thyroid ablation. Local myxedema or bone changes of acropachy may not be recognized on clinical examination unless the clinical and roentgenological features are known. Original diagnostic criteria include decreased skin temperature over early local myxedema, and increased width of the diaphysis of distal short bones. Differential diagnoses include acromegaly, pachydermoperiostosis, neurotic arthralgias, and hypertrophic pulmonary osteoarthropathy. Local trauma may determine the site of acral changes.
Inflammation, Pravastatin, and the Risk of Coronary Events After Myocardial Infarction in Patients With Average Cholesterol Levels
Authors: Paul M. Ridker, Nader Rifai, Marc A. Pfeffer, Frank M. Sacks, Lemuel A. Moye, Steven Goldman, Greg C. Flaker, Eugene Braunwald
Journal: Circulation (1998)

We studied whether inflammation after myocardial infarction (MI) is a risk factor for recurrent coronary events and whether randomized treatment with pravastatin reduces that risk.A nested case-control design was used to compare C-reactive protein (CRP) and serum amyloid A (SAA) levels in prerandomization blood samples from 391 participants in the Cholesterol and Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal coronary event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (control subjects). Overall, CRP and SAA were higher among cases than control subjects (for CRP P=0.05; for SAA P=0.006) such that those with levels in the highest quintile had a relative risk (RR) of recurrent events 75% higher than those with levels in the lowest quintile (for CRP RR= 1.77, P=0.02; for SAA RR= 1.74, P=0.02). The study group with the highest risk was that with consistent evidence of inflammation (elevation of both CRP and SAA) who were randomly assigned to placebo (RR=2.81, P=0.007); this risk estimate was greater than the product of the individual risks associated with inflammation or placebo assignment alone. In stratified analyses, the association between inflammation and risk was significant among those randomized to placebo (RR=2.11, P=0.048) but was attenuated and nonsignificant among those randomized to pravastatin (RR=1.29, P=0.5).Evidence of inflammation after MI is associated with increased risk of recurrent coronary events. Therapy with pravastatin may decrease this risk, an observation consistent with a nonlipid effect of this agent.
ABNORMAL CORONARY VASOMOTION IN PATIENTS WITH UNOBSTRUCTED CORONARY ARTERIES IS ASSOCIATED WITH BIOMARKERS OF INFLAMMATION, ENDOTHELIAL FUNCTION AND PLATELET ACTIVATION
Authors: Peter Ong, Anastasios Athanasiadis, Amelia Carro Hevia, Dieter Ratge, Gabor Borgulya, David Gaze, Udo Sechtem, Juan Carlos Kaski
Journal: Journal of the American College of Cardiology (2011)
Wernicke Encephalopathy Following Prolonged Intravenous Therapy
Authors: Alan M. Nadel
Journal: JAMA (1976)

Two nonalcoholic patients who were maintained for extended periods on intravenous fluids manifested the morphologic expressions of Wernicke encephalopathy. A thiamine-deficiency state was not suspected and vitamins were never administered. These cases emphasize the consequences of this disorder and the rapidity with which the state of thiamine depletion can develop. (<i>JAMA</i>235:2403-2405, 1976)
Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.
Authors: T Schneider, H U Jahn, W Schmidt, E O Riecken, M Zeitz, R Ullrich
Journal: Gut (1995)

Although changes in T lymphocyte subset distribution in the peripheral blood of patients infected with human immunodeficiency virus (HIV) are well defined it is not known whether these changes reflect changes in lymphoid compartments clearly involved in HIV related disease like the intestinal mucosa. This study analysed lymphocytes isolated simultaneously from the peripheral blood and duodenal biopsy specimens by three colour flow cytometry in eight asymptomatic HIV infected patients, 26 AIDS patients, and 23 controls. The proportion of CD4, CD8, CD4-CD8-, or gamma delta T cells did not correlate between circulating and duodenal T cells. CD4 T cells were reduced in the peripheral blood (7.5% (25th-75th percentile, 2-16%) v 52% (41-63%), p &lt; 0.0005) and even more reduced in the duodenum (1% (1-2%) v 36% (23-57%), p &lt; 0.0005) of AIDS patients compared with controls. Patients with asymptomatic HIV infection had intermediate CD4 T cells in the peripheral blood (24% (22-35%); p &lt; 0.002 v controls; p &lt; 0.01 v AIDS) but like AIDS patients very low CD4 T cells in the duodenum (3% (1-6%); p &lt; 0.002 v controls). The ratio of duodenal to circulating CD4+ T cells was significantly reduced to 0.2 (0-1) in AIDS patients (p &lt; 0.001) and even to 0.1 (0.04-0.5) in asymptomatic HIV infected patients (p &lt; 0.002) compared with 0.72 (0.44-0.95) in controls. These findings show an early and preferential loss of duodenal CD4 T cells in HIV infection. Immunological abnormalities in HIV infection are distinct between lymphoid compartments, and profound immunodeficiency may occur in the intestinal immune system although circulating T cells are largely preserved.
Acute effect of oral phosphate loading on serum fibroblast growth factor 23 levels in healthy men
Authors: Y. Nishida, Y. Taketani, H. Yamanaka-Okumura, F. Imamura, A. Taniguchi, T. Sato, E. Shuto, K. Nashiki, H. Arai, H. Yamamoto, E. Takeda
Journal: Kidney International (2006)
Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-Alpha in Myocardium in Human Dilated Cardiomyopathy
Authors: Mamoru Satoh, Motoyuki Nakamura, Gen Tamura, Shinji Makita, Ikuo Segawa, Atsushi Tashiro, Ryoichi Satodate, Katsuhiko Hiramori
Journal: Journal of the American College of Cardiology (1997)
EARLY EFFECTS OF FASTING AND OF CARBOHYDRATE INGESTION ON LIPIDS AND LIPOPROTEINS OF SERUM IN MAN
Authors: Richard J. Havel
Journal: Journal of Clinical Investigation (1957)

It is generally assumed that plasma lipoproteins function as carriers in the transport of fatty acids to and from the liver, fat depots, and peripheral tissues, but the roles of the various lipoprotein classes in this regard are not established. A previous study showed that the concentration of triglycerides in serum was lower several hours after the ingestion of a meal containing no fat than after an overnight fast (1). In the present study large quantities of glucose were fed to fasting young adults; the resulting alterations in various lipid constituents of ultracentrifugally separated lipoprotein classes were compared with changes observed during comparable periods of continued fasting. These comparisons showed that the concentrations of all major lipid constituents of the very low density lipoproteins of serum fall significantly after the ingestion of glucose. This finding suggests that very low density lipoproteins have a significant role in the transport of fatty acids derived from endogenous sources.