tbuckley/cabot-search huggingface dataset:
Gene Therapy for Malignant Glioma: Current Clinical Status
Authors: Kalevi J. Pulkkanen, Seppo Yla-Herttuala
Journal: Molecular Therapy (2005)

Glioblastoma is an aggressive brain tumor with a dismal prognosis. Gene therapy may offer a new option for the treatment of these patients. Several gene therapy approaches have shown anti-tumor efficiency in experimental studies, and the first clinical trials for the treatment of malignant glioma were conducted in the 1990s. HSV-tk gene therapy has been the pioneering and most commonly used approach, but oncolytic conditionally replicating adenoviruses and herpes simplex virus mutant vectors, p53, interleukins, interferons, and antisense oligonucleotides have also been used. During the past few years, adenoviruses have become the most popular gene transfer vectors, and some recent randomized, controlled trials have shown significant anti-tumor efficacy in clinical use. However, efficient gene delivery into the brain still presents a major problem, and there is a lack of definitive phase III trials, which would avoid potential problems associated with a small number of patients, inadvertent patient selection, and overinterpretation of results based on a few long-time survivors. For clinical efficacy, median survival is one of the most rigorous endpoints. It is used here to evaluate the usefulness of various treatment approaches and current clinical status of gene therapy for malignant glioma.
Carcinoma of the gastric stump: risks and pathogenesis.
Authors: T C Northfield, C N Hall
Journal: Gut (1990)

Carcinoma of the gastric stump: risks and pathogenesis Gastric carcinoma occurring five or more years after gastric surgery for benign disease is now widely recognised as a distinct clinical entity -gastric stump carcinoma.The earlier appearance of cancer questions the true nature of the original preoperative disease and it is, therefore, discounted.Historically, carcinoma of the gastric stump is most closely associated with simple gastroenterostomy and Billroth II gastrectomy,' 2 but this may simply reflect that these were the most popular surgical treatments for peptic ulcer disease.Stump cancer can occur with similar frequency after the less common Billroth I gastrectomy3 and with truncal vagotomy and drainage procedures4; cases of this complication after highly selective vagotomy5 are now being reported.Gastric surgery and gastric cancer Controversy surrounds the relation between gastric surgery and gastric cancer: is gastric surgery a causative factor in the carcinogenic process or is the association purely coinci- dental?The most carefully controlled data on this subject relate to animal experiments with and without administration of initiating carcinogens.With few exceptions these data show that operations which promote duodenogastric bile reflux increase the susceptibility of the stomach to neoplastic change.67Conversely, the oral administration of bile acids with initiating carcinogens enhances tumour yield in the non- operated stomach.8Thus, experimentally at least, gastric surgery seems to promote gastric carcinogenesis by mecha- nisms which involve bile reflux.Human data are inevitably much less consistent and reliable epidemiological studies suggest that achlorhydria and atrophic gastritis are factors
Book Review Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach Second edition. Edited by Cindy L. Schwartz, Wendy L. Hobbie, Louis S. Constine, and Kathleen S. Ruccione. 348 pp., illustrated. Berlin, Springer-Verlag, 2005. $129. 3-540-40840-1
Authors: Ching-Hon Pui
Journal: New England Journal of Medicine (2005)
Sierra Leone's maternal mortality rate is a "human rights emergency"
Authors: P. Moszynski
Journal: BMJ (2009)

One in eight women in Sierra Leone risk dying during pregnancy or childbirth, says a report from Amnesty International. The charity’s secretary general, Irene Khan, said that this was partly due to the “extremely low status” of women in rural areas and was explicitly linked to the lack of women’s rights.

Lack of medical facilities and transport in many districts mean that a skilled birth attendant is present at less than half of deliveries in Sierra Leone and that less than a fifth of deliveries take place in healthcare facilities. However, “underlying the issue is the denial and neglect of maternal mortality in a male-dominated society,” says the report.

Ms Khan explained: “In rural areas women …
The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle cell proliferation and re-endothelialization.
Authors: R J Friedman, M B Stemerman, B Wenz, S Moore, J Gauldie, M Gent, M L Tiell, H Spaet
Journal: Journal of Clinical Investigation (1977)

This study was designed to investigate the mechanisms involved in fibromusculoelastic lesion formation produced by selective de-endothelialization by the intra-arterial balloon catheter technique in thrombocytopenic rabbits. Thrombocytopenia was induced and maintained for up to 30 days by daily injections fo highly specific sheep anti-rabbit platelet sera (APS). Evidence for re-endothelialization was obtained by i.v. Evans blue dye 30 min before sacrifice. Rabbits received daily injections of APS, which reduced the mean platelet count to 5,600/cm3; control animals received identically treated normal sheep sera on the same schedule, and had mean daily platelet counts of 363,000/cm3. Evaluation of intimal thickness was assessed by counting cell layers in semithin sections. Intimal thickening in aortae from rabbits treated with APS was strikingly suppressed, in contrast to those from normal sheep sera-treated animals which showed a mean intimal thickness of 18 cell layers within 28 days often after de-endothelialization. Re-endothelialization was not affected by APS treatment. These results indicate that the proliferation of smooth muscle cells is dramatically inhibited by reduction of platelets.
Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment
Authors: Michael J. Elman, Haijing Qin, Lloyd Paul Aiello, Roy W. Beck, Neil M. Bressler, Frederick L. Ferris, Adam R. Glassman, Raj K. Maturi, Michele Melia
Journal: Ophthalmology (2012)
The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog.
Authors: S F Khuri, R A Kloner, S A Karaffa, W Marston, A D Taylor, N C Lai, D E Tow, E M Barsamian
Journal: Circulation Research (1985)

After acute regional coronary occlusion, myocardial tissue PCO2, as measured by mass spectrometry, rises, reaches a peak, and then gradually falls. This late fall in myocardial tissue PCO2 could be due to (1) a gradual increase in tissue blood flow (and hence improved carbon dioxide washout), (2) a gradual consumption of tissue bicarbonate, (3) a gradual reduction in the production of carbon dioxide due to progressive cellular damage, or (4) an artifact caused by the continued presence of the mass spectrometer probe in the ischemic tissue. To determine which of these four mechanisms is responsible for the late fall in myocardial tissue PCO2, we subjected 27 anesthetized open-chest dogs to 3-hour occlusion of the left anterior descending coronary artery. Both myocardial tissue PCO2 and intramyocardial hydrogen ion concentration were measured in the myocardial segment supplied by the left anterior descending coronary artery. Ten dogs (group 1) were killed after the occlusion (occlusion I), and 11 dogs (group 2) underwent reocclusion (occlusion II) at the same site after a 45-minute period of reflow. Regional myocardial blood flow was measured periodically by the intramural injection of 127Xe. Changes in myocardial tissue PCO2 and hydrogen ion concentration were related to ultrastructural changes in the tissues adjacent to the myocardial tissue PCO2 probe. Regional myocardial blood flow remained unchanged throughout the 3-hour occlusion, ruling out increased carbon dioxide washout as a cause for its late fall. Tissue hydrogen ion concentration, as measured by a new lead glass electrode, correlated well with myocardial tissue PCO2, with the reduction in regional myocardial blood flow, and with ischemic damage assessed histologically. Myocardial hydrogen ion concentration also exhibited a late fall after the occlusion, from a peak of 199.8 +/- 27.8 nmol/liter to 91.9 +/- 12.1 nmol/liter (mean +/- SEM). This ruled out consumption of tissue bicarbonate as the cause for the late fall in myocardial tissue PCO2. Peak rise in myocardial tissue PCO2 after occlusion II (71.2 +/- 7.9 mm Hg) was significantly lower than peak myocardial tissue PCO2 after occlusion I (116.7 +/- 13.9 mm Hg, P less than 0.001). The difference between these latter two values, as well as the magnitude of fall in myocardial tissue PCO2 during occlusion I, related directly to the degree of histological damage observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis
Authors: Orlando M. Gutiérrez, Michael Mannstadt, Tamara Isakova, Jose Alejandro Rauh-Hain, Hector Tamez, Anand Shah, Kelsey Smith, Hang Lee, Ravi Thadhani, Harald Jüppner, Myles Wolf
Journal: New England Journal of Medicine (2008)

Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown.
Ca-dependence of isometric force kinetics in single skinned ventricular cardiomyocytes from rats
Authors: C. Vannier, H. Chevassus, G. Vassort
Journal: Cardiovascular Research (1996)

The effects of Ca2+ on the rate of tension redevelopment following a brief release/restretch were investigated in single chemically-skinned ventricular myocytes from the rat.The myocytes were enzymatically isolated and skinned using Triton-X100. They were then attached with an optical adhesive glue to glass micropipettes fixed to a piezoelectric translator and a force transducer. Tension redevelopment was measured at various levels of Ca activation after disrupting force-generating crossbridges by a brief (20 ms) step release/restretch equivalent to 20% of the original 2.1 microns sarcomere length. Most of tension redevelopment was well fitted by a monoexponential function.At maximal Ca concentrations, pCa 4.5 maximal force was obtained at 2.1 microns sarcomere length and averaged 11.8 +/- 0.7 microN. The rate of tension redevelopment (ktr) increased with increasing Ca concentrations up to 5.19 +/- 0.37.s-1 at maximal Ca activation. The relation between the rate of tension redevelopment and Ca concentration was sigmoidal and could be fitted by the Hill equation with coefficients similar to those describing the tension-pCa relation. The relation between relative rate of tension redevelopment and relative steady activated tension was curvilinear increasing with increasing Ca concentration.In cardiac muscle, Ca2+ modulates both the number and the kinetics of force-generating crossbridges in a manner similar to that previously reported in skeletal muscle.
Chemically Induced Birth Defects
Authors: José F. Cordero
Journal: JAMA (1986)

More pregnant women are becoming concerned about the adverse effects that might result from exposure to chemicals in the environment. This has resulted in an ever-increasing number of inquiries to physicians about the possible teratogenicity of chemicals and drugs. Unfortunately, few references and few human data are available for use in responding to such inquiries. This book is an excellent and welcome summary of the literature on studies in humans and animals of exposures to drugs and chemicals. The text is organized by categories of drugs and chemicals; an index includes generic names and some of the most commonly used trade names. Each chapter has a detailed summary of the data available from human experience and animal studies. One of the book's most important features is the review of adverse reproductive outcomes related to chemical exposure. An introductory chapter on chemical exposures during pregnancy gives a historical perspective on the
Financial Incentives to Physicians
Authors: Richard H. Egdahl, Cynthia H. Taft
Journal: New England Journal of Medicine (1986)

Physicians are under increasing pressure from hospitals and managed care plans to practice more efficiently. The focus is no longer on a minority of outliers but instead on the practice patterns of most physicians, since it is recognized that large savings are possible only when doctors as a group move in the direction of greater efficiency.The challenge is to find appropriate ways to change physicians' practice patterns. Historically, doctors have resisted change initiated by those outside the medical profession. This resistance results not only from habits acquired in medical school and residency training but also from the ethical tenet . . .
Intracardiac Extension of Lung Cancer Demonstrated on PET Scanning
Authors: Gary F. Gates, Amy Aronsky, Hasan Ozgur
Journal: Clinical Nuclear Medicine (2006)

Intracardiac tumors are unusual and can originate within the heart or spread from other sites. This is a report of a patient who presented with a TIA, and during the subsequent stroke workup, a right hilar nonsmall cell lung carcinoma was discovered. The tumor had extended into the left atrium through a pulmonary vein. The hilar tumor as well as intracardiac extension were demonstrated by PET scanning using FDG.
Juvenile Pernicious Anaemia and Hypothyroidism. A Family Study
Authors: R. A. M. Oliver, G. P. Baker
Journal: BMJ (1969)

A man presented with the sudden onset of pernicious anaemia at the age of 21. He had been treated for hypothyroidism since the age of 6. His father and only paternal aunt were also found to have pernicious anaemia. Gastric and thyroid antibody studies showed one or more antibodies to be present in all three subjects, as well as in the patient's mother.
Action of Pure Ethanol and Some Alcoholic Beverages on the Gastric Mucosa in Healthy Humans: A Descriptive Endoscopic Study
Authors: M. R. Knoll, C. B. Kölbel, S. Teyssen, M. V. Singer
Journal: Endoscopy (1998)

Background and Study Aims: The action of ethanol and alcoholic beverages on the gastric mucosa in healthy humans is largely unknown. This study was designed to compare the effects of beer, white wine, whisky, and the comparable pure ethanol solutions on the gastric and duodenal mucosa in a controlled, randomized, doubleblind endoscopic investigation.
Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function
Authors: Juliette Martin, Olivier Maurhofer, Nadège Bellance, Giovanni Benard, Franziska Graber, Dagmar Hahn, Anne Galinier, Caroline Hora, Anirudh Gupta, Gisèle Ferrand, Hans Hoppeler, Rodrigue Rossignol, Jean-François Dufour, Marie V. St-Pierre
Journal: Hepatology (2012)

The histidine triad nucleotide-binding (HINT2) protein is a mitochondrial adenosine phosphoramidase expressed in the liver and pancreas. Its physiological function is unknown. To elucidate the role of HINT2 in liver physiology, the mouse Hint2 gene was deleted. Hint2 −/− and Hint2 +/+ mice were generated in a mixed C57Bl6/J × 129Sv background. At 20 weeks, the phenotypic changes in Hint2 −/− relative to Hint2 +/+ mice were an accumulation of hepatic triglycerides, decreased tolerance to glucose, a defective counter-regulatory response to insulin-provoked hypoglycemia, and an increase in plasma interprandial insulin but a decrease in glucose-stimulated insulin secretion and defective thermoregulation upon fasting. Leptin messenger RNA (mRNA) in adipose tissue and plasma leptin were elevated. In mitochondria from Hint2 −/− hepatocytes, state 3 respiration was decreased, a finding confirmed in HepG2 cells where HINT2 mRNA was silenced. The linked complex II-III electron transfer was decreased in Hint2 −/− mitochondria, which was accompanied by a lower content of coenzyme Q. Hypoxia-inducible factor-2α expression and the generation of reactive oxygen species were increased. Electron microscopy of mitochondria in Hint2 −/− mice aged 12 months revealed clustered, fused organelles. The hepatic activities of 3-hydroxyacyl-coenzyme A dehydrogenase short chain and glutamate dehydrogenase (GDH) were decreased by 68% and 60%, respectively, without a change in protein expression. GDH activity was similarly decreased in HINT2-silenced HepG2 cells. When measured in the presence of purified sirtuin 3, latent GDH activity was recovered (126% in Hint2 −/− versus 83% in Hint2 +/+). This suggests a greater extent of acetylation in Hint2 −/− than in Hint2 +/+. Conclusion : Hint2/HINT2 positively regulates mitochondrial lipid metabolism and respiration and glucose homeostasis. The absence of Hint2 provokes mitochondrial deformities and a change in the pattern of acetylation of selected proteins.
Plasma Testosterone and Testosterone Binding Affinities in Men with Impotence, Oligospermia, Azoospermia, and Hypogonadism
Authors: D. M. Lawrence, G. I. M. Swyer
Journal: BMJ (1974)

Mean plasma testosterone levels (± S.D.), using Sephadex LH-20 and competitive protein binding, were 629 ± 160 ng/100 ml for a group of 27 normal adult men, 650 ± 205 ng/100 ml for 27 impotent men with normal secondary sex characteristics, 644 ± 178 ng/100 ml for 20 men with oligospermia, and 563 ± 125 ng/100 ml for 16 azoospermic men. None of these values differ significantly. For 21 men with clinical evidence of hypogonadism the mean plasma testosterone (± S.D.), at 177 ± 122 ng/100 ml, differed significantly (P &lt; 0·001) from that of the normal men. The mean testosterone binding affinities (as measured by the reciprocal of the quantity of plasma needed to bind 50% of <sup>3</sup>H-testosterone tracer) were similar for normal, impotent, and oligospermic men. Though lower for azoospermic men the difference was not significant (P &gt;0·1). For 12 of the 16 hypogonadal males the testosterone binding affinity was normal, but raised binding affinities, similar to those found in normal adult females or prepubertal boys (about twice normal adult male levels), were found in four cases of delayed puberty. These findings help to explain why androgen therapy is usually useless in the treatment of impotence.
Professionalism must be taught
Authors: S. R Cruess, R. L Cruess
Journal: BMJ (1997)

Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. <b>Methods:</b> Male Wistar rats (4 per group) were injected intravenously with 1 MBq of <sup>111</sup>In-labeled octreotide (OCT), minigastrin (MG), bombesin (BOM), or exendin (EX), together with a potential inhibitor of renal uptake (lysine [Lys], poly-glutamic acid [PGA], and Gelofusine [GF], a gelatin-based plasma expander) or phosphate-buffered saline as a control. Organ uptake at 20 h after injection was determined as the percentage of injected activity per gram (%IA/g). Lys, PGA, and GF were also combined to determine whether an additive effect could be obtained. The localization of the peptides in the kidneys was investigated by autoradiography using a phosphor imager. <b>Results:</b> OCT accumulation in the kidney was inhibited by Lys and GF (40.7%–45.1%), whereas PGA was ineffective. On the other hand, renal uptake of BOM, MG, and EX was inhibited by PGA and GF (15.4%–85.4%), whereas Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting OCT uptake, whereas PGA and GF had additive effects for the inhibition of EX uptake. The amount of kidney uptake correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex, as indicated by autoradiography. <b>Conclusion:</b> Inhibition of renal accumulation of the radiopeptides tested could be achieved by either Lys or PGA but not by both at the same time, suggesting 2 different uptake mechanisms. The differences in renal accumulation of radiopeptides may be related to the number of charges of a molecule. GF is the only compound that inhibited renal accumulation of all radiopeptides tested. Additional experiments are needed to further elucidate these findings and to optimize inhibition of renal accumulation of radiopeptides to reduce the kidney dose in PRRT.
Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance Heralds an Adverse Prognosis in Nonischemic Cardiomyopathy
Authors: Katherine C. Wu, Robert G. Weiss, David R. Thiemann, Kakuya Kitagawa, André Schmidt, Darshan Dalal, Shenghan Lai, David A. Bluemke, Gary Gerstenblith, Eduardo Marbán, João A.C. Lima, Gordon F. Tomaselli
Journal: Journal of the American College of Cardiology (2008)
The Total Artificial Heart as a Bridge to Transplantation
Authors: Jack G. Copeland
Journal: JAMA (1986)

In 1985, at the University of Arizona, Tucson, two attempts were made to "bridge" patients from impending death to heart transplantation, using orthotopically positioned total artificial hearts. The first attempt, using an unapproved device on an emergency basis, failed after transplantation because of severe pulmonary edema and Pseudomonas pneumonia and the apparent transmission of a Pseudomonas infection from donor to recipient. The second experience, using a Jarvik-7 device, led to stable support for nine days with one major complication, a reversible neurologic deficit with no associated computed tomographic scan abnormality. This patient survived cardiac transplantation and, after being successfully treated for complications, has made a full recovery and returned to full-time work.
Alexander of Abonoteichus
Authors: Adrian W. Zorgniotti
Journal: JAMA (1973)

Toward the end of the second century AD, the satirist Lucian scathingly attacked a daring and intelligent charlatan, Alexander, who came from Abonoteichus in Asia. In addition to Lucian's writings, archeologic and numismatic finds attest the way the fame of Alexander and his oracular serpent, Glykon, spread throughout a large part of the Roman world. But not until we read Lucian's story,<i>Alexander the False Magician</i>, does he emerge, very much alive, as the unscrupulous founder of an Asclepian cult at a time when orthodox paganism was in decline. Glykon was no ordinary healing serpent, since he spoke oracles which, when they backfired, sent shock waves as far as the Imperial Throne of Marcus Aurelius himself! The recent discovery of a bronze statuette of Glykon during excavation of the Athenian Agora further exemplifies the way that artefacts confirm statements by ancient authors. Alexander, born in the Black Sea city of
Is There a Problem With Enhancement?
Authors: Frances M. Kamm
Journal: The American Journal of Bioethics (2005)

This article examines arguments concerning enhancement of human persons recently presented by Michael Sandel (2004). In the first section, I briefly describe some of his arguments. In section two, I consider whether, as Sandel claims, the desire for mastery motivates enhancement and whether such a desire could be grounds for its impermissibility. Section three considers how Sandel draws the distinction between treatment and enhancement, and the relation to nature that he thinks each expresses. The fourth section examines Sandel's views about parent/child relations and also how enhancement would affect distributive justice and the duty to aid. In conclusion, I briefly offer an alternative suggestion as to why enhancement may be troubling and consider what we could safely enhance.
Risk-factors for acquisition of extended-spectrum β-lactamase-producing Escherichia coli among hospitalised patients
Authors: C. Peña, C. Gudiol, F. Tubau, M. Saballs, M. Pujol, M.A. Dominguez, L. Calatayud, J. Ariza, F. Gudiol
Journal: Clinical Microbiology and Infection (2006)