tbuckley/cabot-search huggingface dataset:
Coordinacy of lysosomal enzyme excretion in human urine.
Authors: K Paigen, J Peterson
Journal: Journal of Clinical Investigation (1978)

Assay conditions have been developed for the determination of urinary beta-glucuronidase, beta-galactosidase, alpha-galactosidase, and beta-hexosaminidase using fluorometric substrates. The assay conditions for beta-glucuronidase overcome interference by both low and high molecular weight inhibitors, a problem that has confused earlier studies of enzyme excretion. The four lysosomal enzymes are excreted corrdinately: although their absolute levels (in units per milligram of creatinine) vary during the day and from one day to the next, the ratio of one enzyme to another remains relatively constant. The lack of correlation betweem plasma and urine enzyme levels, together with the high molecular weights of these enzymes, suggests that the urinary enzymes are not derived by glomerular filtration. The lack of coordinacy with lactate dehydrogenase suggests they are not derived from exfoliated cells. by analogy with experimental animals, they may be derived from lysosomes extruded into the lumen of the proximal tubule by epithelial cells. There is considerable variation among a population of 125 healthy adult subjects for total enzyme excretion. Both total enzyme excretion and coordinacy ratios are log-normally distributed, suggesting that they are the resultants of many factors, each of which has a relative, or proportional, effect on enzyme excretion. About one-half the population variation resides in a process common to the excretion of all four enzymes (possibly the lysosome extrusion pathway), and about one-half resides in factors affecting each enzyme independently.
The New Recommendations on Duty Hours from the ACGME Task Force
Authors: Thomas J. Nasca, Susan H. Day, E. Stephen Amis
Journal: New England Journal of Medicine (2010)

A task force of the Accreditation Council for Graduate Medical Education (ACGME) has proposed modifications in the current requirements for medical residency training programs, including in the limits on resident hours. This article explains the proposed changes and the rationale for them and invites input on the new requirements, which are scheduled for implementation in 2011.
Nerve Symptoms in Vertebral Rheumatism
Authors: C. W. Buckley
Journal: Annals of the Rheumatic Diseases (1945)

It is widely assumed by the general public that if assisted suicide (AS) or euthanasia (VE) were legalised doctors must be essentially involved in the whole process including prescribing the medication and (in euthanasia) administering it. This paper explores some reasons for this assumption and argues that it flatly contradicts what it means to be a doctor. The paper is thus not mainly concerned with the ethics of AS/VE but rather with the concept of a doctor that has evolved since the time of Hippocrates to current professional guidance reflected in healthcare law. The paper argues that the most common recent argument for AS/VE – that patients have a right to control when and how they die – in fact points to the involvement not of doctors but of legal agencies as decision makers plus technicians as agents.
591 TRANS ARTERIAL CHEMO-EMBOLIZATION (TACE) IS A SAFE AND EFFECTIVE TREATMENT FOR VERY ELDERLY PATIENTS WITH HEPATOCELLULR CARCINOMA (HCC)
Authors: M.J. Cohen, I. Levy, D. Shouval, T. Nesher, A.I. Bloom, O. Shibolet
Journal: Journal of Hepatology (2010)
Sustained Suppression of Ischemic Complications of Coronary Intervention by Platelet GP IIb/IIIa Blockade With Abciximab
Authors: A. Michael Lincoff, James E. Tcheng, Robert M. Califf, Dean J. Kereiakes, Thomas A. Kelly, Gerald C. Timmis, Neal S. Kleiman, Joan E. Booth, Craig Balog, Catherine F. Cabot, Keaven M. Anderson, Harlan F. Weisman, Eric J. Topol
Journal: Circulation (1999)

Background —Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. Methods and Results —A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group ( P &lt;0.001), and 9.5% in the abciximab with standard-dose heparin group ( P &lt;0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. Conclusions —Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.
Doctor resigns after wrong diagnoses
Authors: C Essex
Journal: BMJ (1994)

A New Zealand pathologist has retired on grounds of ill health following confirmation of the wrong diagnosis of more than 50 cancer patients. Surgeons at Wanganui Hospital raised concerns about unexpected biopsy results from Dr James Burkinshaw. An independent laboratory assessment confirmed the misdiagnosis, and Dr Burkinshaw resigned the following day. About half the patients were told they had cancer when they did not, and the remainder were wrongly diagnosed as not having cancer. Five women had unnecessary mastectomies and one woman had an unnecessary …
Hierarchies in Neurology: A Reappraisal of a Jacksonian Concept
Authors: Frank R. Freemon
Journal: JAMA (1989)

In the late 19th century, John Hughlings Jackson advanced the hypothesis that the central nervous system works by means of hierarchies. Although the theory was highly nuanced and complex, its predominant theme held that damage to nervous tissue that made up the highest system caused the brain to revert to a more primitive mode of operation. If a disease or lesion was followed by a certain loss, the physician should not conclude that the lost ability was resident in the damaged region, but rather that the highest system no longer operated and the remaining brain as a whole was working at a more primitive level. In some formulations of his theory, Jackson correlated the dissolution of nervous system hierarchies with presumed stages of phylogenetic development according to the Darwinian theory of evolution. In 1985, a group of neurologists and neuroscientists gathered in London to observe the 150th anniversary of Jackson's
P54 Impact of a rapid access system for early referral of suspected TB cases
Authors: R. Verma, J. Lee, P. Haldar, G. Woltmann
Journal: Thorax (2011)

<h3>Introduction</h3> Early diagnosis and treatment of infectious tuberculosis (TB) is an important strategy for controlling the burden of disease by minimising the spread of infection and secondary disease in close contacts. Since 2005, we have developed a centralised rapid referral system in Leicester for the early assessment of suspected TB by a specialist physician. The system is triggered by a list of “red-flag” symptoms submitted on a proforma and/or appropriate coding by the reporting radiologist of all abnormal chest radiographs compatible with a possible diagnosis of TB. <h3>Aims</h3> To evaluate whether differences exist in disease characteristics and time to diagnosis with availability of the rapid referral system. <h3>Methods</h3> A retrospective analysis of data collected from patients referred to the Rapid Access TB clinic between the years 2005 and 2010 was conducted. A sub-group analysis was completed for the years 2007–2009 comparing cases referred to the rapid access clinic with those diagnosed by other (non-rapid referral) pathways. <h3>Results</h3> 1552 suspected cases of tuberculosis were referred through the rapid access system, with a positive diagnosis made in 566 (36.5%). Radiological coding of CXR reports was the primary trigger for 93.8% of referrals. No differences existed in age, gender or ethnicity of patients identified through rapid access or other pathways. A significantly higher proportion of cases identified through rapid access were pulmonary (Abstract P54 table 1). The rapid access system was associated with a significant reduction in the time to specialist assessment for both non-pulmonary and smear positive pulmonary TB. <h3>Conclusions</h3> A rapid access system of referral that incorporates a red-flag coding system of potentially abnormal CXRs effectively identifies a significant proportion of pulmonary TB cases and reduces the time to assessment and treatment of smear positive pulmonary TB.
Current Management of Scaphoid Fractures: Twenty Questions Answered
Authors: T Lasoye
Journal: Journal of the Royal Society of Medicine (2003)

In an article a decade ago, Nicholas Barton posed twenty key questions about the management of scaphoid fractures. Here, experts from Europe, America, Australia and Japan respond to the questions, rephrased by Izge Gunal and Ismail Calli. The text resembles a panel discussion, with Barton the moderator and Gunal and Calli the scribes. The question—discussion—comment format covers diagnosis, imaging, treatment and complications. Each section is well illustrated with diagrams and images. Barton tries to emphasize the points of agreement and to explain the not infrequent disagreement between contributors. The division by questions means that readers can readily focus on aspects that relate most to their practice. However, anyone seeking prescriptive answers will be disappointed: the information on diagnostic and treatment options is presented in a mixture of research outcomes and anecdote. The book is certainly useful in revealing areas of ambiguity that could be clarified by further research; there are, of course, many more than twenty questions to be answered. The style and format will have its fans, but some readers might prefer less emphasis on personal views and a more scientific write-up.
A NEW DUODENAL TIP
Authors: Carl V. Vischer
Journal: JAMA (1926)

After having used a number of the standard duodenal tubes, such as those of Jutte, Rehfuss, Lyon and Einhorn, with the aid of my brother and associate, Dr. Thomas J. Vischer, I designed a duodenal tip as shown in the accompanying illustration. The tip is ¾ inch (2 cm.) in length, ¼ inch (0.6 cm.) in diameter, 11/64 inch at the threaded end and the caliber, 3/32 inch. There are five drain holes placed as shown in the illustration, each 0.067 inch in diameter and countersunk. The tip may be used on any standard tube. We have used the tip on both the Jutte and Rehfuss tubes. It weighs exactly 2.75 Gm.; it is made of German silver and is double gold plated. After having constantly used the tip over a period of time, I have noted the following advantages: The tube is more easily introduced; it is never necessary
Insulin-Like Growth Factors and Hematologic Malignancies
Authors: Ilan Shimon
Journal: Annals of Internal Medicine (1995)

Letters1 July 1995Insulin-Like Growth Factors and Hematologic MalignanciesIlan Shimon, MD and Ofer Shpilberg, MDIlan Shimon, MDCedars-Sinai Medical Center; Los Angeles, CA 90048-1865University of Pittsburgh; Pittsburgh, PA 15261Search for more papers by this author and Ofer Shpilberg, MDCedars-Sinai Medical Center; Los Angeles, CA 90048-1865University of Pittsburgh; Pittsburgh, PA 15261Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-1-199507010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their excellent review on the family of insulin-like growth factors (IGF) and cancer, LeRoith and colleagues [1] described the current knowledge of the role of the IGFs and of their receptors and binding proteins in certain solid tumors. However, the authors did not mention the involvement of the IGF system in the growth and development of neoplastic hematologic processes. We recently reviewed the relevant literature on the role of the IGF system in the regulation of normal and malignant hematopoiesis [2]. Nearly all hematopoietic cells, either normal or neoplastic, express the receptors of IGF, and some ...References1. LeRoith D, Baserga R, Helman L, Roberts CT Jr. Insulin-like growth factors and cancer. Ann Intern Med. 1995; 122:54-9. Google Scholar2. Shimon I, Shpilberg O. The insulin-like growth factor system in regulation of normal and malignant hematopoiesis. Leuk Res. 1995; 19:233-40. Google Scholar3. Sinclair J, McClain D, Taetle R. Effects of insulin and insulin-like growth factor I on growth of human leukemia cells in serum-free and protein-free medium. Blood. 1988; 72:66-72. Google Scholar4. Oksenberg D, Dieckmann BS, Greenberg PL. Functional interactions between colony-stimulating factors and the insulin family hormones for human myeloid leukemic cells. Cancer Res. 1990; 50:6471-7. Google Scholar5. Correa PN, Eskinazi D, Axelrod AA. Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium. Blood. 1994; 83:99-112. Google Scholar Author, Article, and Disclosure InformationAffiliations: Cedars-Sinai Medical Center; Los Angeles, CA 90048-1865University of Pittsburgh; Pittsburgh, PA 15261 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia 1 July 1995Volume 123, Issue 1Page: 76KeywordsAcute myeloid leukemiaB cellsCellsGrowth factorsHereditary nonpolyposis colorectal cancerInsulin-like growth factorsPolycythemia veraPrecursor cellsProteinsT cell receptors Issue Published: 1 July 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Increase of deoxycholate in supersaturated bile of patients with cholesterol gallstone disease and its correlation withde novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and small intestinal transit
Authors: Junichi Shoda, Bing-Fang He, Naomi Tanaka, Yasushi Matsuzaki, Toshiaki Osuga, Shunji Yamamori, Hiroshi Miyazaki, Jan Sjövall
Journal: Hepatology (1995)

A total of 100 nonobese and normolipidemic subjects (29 control subjects, 49 patients with cholesterol stones [CSs], and 22 patients with brown pigment stones) were studied to elucidate the pathogenetic contributions of deoxycholate (DC) to supersaturated bile formation with special reference to de novo syntheses of cholesterol and bile acids in the liver. A higher proportion of DC was observed in gallbladder bile from patients with CSs (CSs; 21.7 ± 1.4%, mean ± SEM, vs. control subjects; 10.2 ± 0.9%). Cholesterol saturation in bile was elevated parallel to the increase of DC ( r = 0.48; P = 0.0002), irrespective of the existence of stones. In a comparison between the 52 subjects with increased DC in bile ( &gt; 10% of biliary bile acids) and the 20 subjects without the increase ( &lt; 10%), the molar percentage of cholesterol in bile was significantly higher in the former (9.4 ± 0.5%) than in the latter (6.7 ± 0.4%) ( P &lt; 0.001). Consistent with the decrease in steady-state level of low-density lipoprotein (LDL) receptor—messenger RNA (mRNA), the catalytic activity and mRNA level of microsomal hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for de novo cholesterol synthesis, were significantly lower in the former (2.9 ± 0.3 pmol/min/mg protein) than in the latter (5.1 ± 0.6) ( P &lt; 0.0001). Biliary molar percentage of bile acids was significantly lower in the former (69.8 ± 1.1%) than in the latter (75.2 ± 1.5%) ( P &lt; 0.01). However, contrary to expectations, the catalytic activity and mRNA level of cholesterol 7α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, were significantly higher in the former (5.8 ± 0.4 pmol/min/mg protein) than in the latter (3.7 ± 0.6) ( P &lt; 0.01). The magnitude of the impaired gallbladder emptying (control subjects; 78.4 ± 4% vs. CSs; 58 ± 3%; P &lt; 0.0005) together with the prolonged small intestinal transit (control subjects; 126 ± 9 minutes vs. CSs; 198 ± 9 minutes; P &lt; 0.01) correlated significantly with the increased percentage of DC in bile. It is concluded that in cholesterol gallstone disease an increase of DC in bile, linked to an impaired gallbladder emptying together with a prolonged small intestinal transit, may play a significant role in downregulating de novo cholesterol synthesis but not bile acid synthesis in the liver. It is further suggested that the formation of supersaturated bile may be attributed to a hypersecretion of cholesterol (derived from an exogeneous source) driven by the flow of DC through the liver, combined with a normosecretion or hyposecretion of bile acids, the pool size of which is reduced because of changes in distribution, e.g., a sequestration into the hypomotile gallbladder and intestine.
Assessment of Serum Levels of MicroRNAs in Patients with Congestive Heart Failure
Authors: Huseyin Altug Cakmak, Hasan Ali Barman, Ender Coskunpinar, Yasemin Musteri Oltulu, Baris Ikitimur, Gunay Can, Vural Ali Vural
Journal: Journal of the American College of Cardiology (2013)
von Willebrand factor binding to platelet GpIb initiates signals for platelet activation.
Authors: M H Kroll, T S Harris, J L Moake, R I Handin, A I Schafer
Journal: Journal of Clinical Investigation (1991)

The hypothesis that von Willebrand factor (vWF) binding to platelet membrane glycoprotein Ib (GpIb) initiates intracellular pathways of platelet activation was studied. We measured the biochemical responses of intact human platelets treated with ristocetin plus vWF multimers purified from human cryoprecipitate. vWF plus ristocetin causes the breakdown of phosphatidylinositol 4,5-bisphosphate, the production of phosphatidic acid (PA), the activation of protein kinase C (PKC), increase of ionized cytoplasmic calcium ([Ca2+]i), and the synthesis of thromboxane A2. PA production, PKC activation, and the rise of [Ca2+]i stimulated by the ristocetin-induced binding of vWF multimers to platelets are inhibited by an anti-GpIb monoclonal antibody, but are unaffected by anti-GpIIb-IIIa monoclonal antibodies. Indomethacin also inhibits these responses without impairing platelet aggregation induced by vWF plus ristocetin. These results indicate that vWF binding to platelets initiates specific intraplatelet signaling pathways. The mechanism by which this occurs involves an arachidonic acid metabolite-dependent activation of phospholipase C after vWF binding to platelet membrane GpIb. This signal then causes PKC activation and increases of [Ca2+]i, which promote platelet secretion and potentiate aggregation.
Reconstructive Surgery of the War Wounded
Authors: Philip D. Wilson
Journal: New England Journal of Medicine (1945)

THE term "reconstructive surgery" means the making good of physical defects. To reconstruct, according to Webster's Dictionary, is "to rebuild, to remodel or to construct again"; hence, the term has a mechanical implication that pertains to a large field of orthopedic surgery. It is a term that was born from the last war after experience with the rebuilding of defects to skin, muscle, nerves, bones and joints resulting from war injuries. It thus has a vital significance today when we have again been at war and confronted with the problem of treating large numbers of battle casualties. My task . . .
The Internalization Route Resulting in Successful Gene Expression Depends on both Cell Line and Polyethylenimine Polyplex Type
Authors: Katharina von Gersdorff, Niek N. Sanders, Roosmarijn Vandenbroucke, Stefaan C. De Smedt, Ernst Wagner, Manfred Ogris
Journal: Molecular Therapy (2006)

Understanding cellular uptake and intracellular processing of nonviral gene delivery systems is a key aspect in developing more efficient vectors. In this study, the impact of clathrin- and caveolae/lipid-raft-dependent endocytosis on cell entry and overall transfection efficiency of polyethylenimine (PEI) polyplexes was evaluated. Most remarkably, the internalization pathway mediating successful transfection depended on both cell type and polyplex type applied. Colocalization studies with transferrin and cholera toxin B revealed that at least two specific endocytosis pathways—the clathrin-dependent and the lipid-raft-dependent—mediated cellular uptake of PEI polyplexes. With the help of specific uptake inhibitors (chlorpromazine and filipin III), cell-line-dependent variations regarding the route of successful transfection were observed (HUH-7, COS-7, HeLa). In COS-7 cells, the clathrin-dependent pathway was the main contributor to the transfection process. In HUH-7 cells, gene transfer by linear PEI polyplexes succeeded mainly via the clathrin-dependent route, whereas transfection by branched PEI polyplexes was mediated by both pathways. In HeLa cells, both pathways were able to mediate successful gene delivery. However, the lipid-raft-dependent pathway was more relevant. The study also revealed that the concentration window between specific inhibitory function and nonspecific toxicity of the uptake inhibitors was very narrow.
Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits.
Authors: S W Fountain, B A Martin, C E Musclow, J D Cooper
Journal: Circulation Research (1980)

Pulmonary leukostasis, as a result of complement activation, has been invoked as a cause of pulmonary dysfunction. To investigate this phenomenon, we studied the pulmonary response to infusion of autologous complement-activated plasma in sheep and rabbits. Complement activation was produced by plasma incubation with zymosan. Leukopenia, with selective loss of polymorphonuclear leukocytes into the lungs, occurred in all animals immediately after the onset of plasma infusion. Complement-activated plasma infusion in sheep produced a significant fall in the arterial PO2 and a marked rise in pulmonary vascular resistance, whereas no such effects were observed in rabbits. Pretreatment of the sheep with sulfinpyrazone eliminated the pulmonary response to complement-activated plasma without altering the leukopenic response. Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfinpyrazone had been administered previously. The pulmonary response to complement activation is associated with pulmonary capillary leukostasis, but leukostasis alone is not an adequate explanation of the phenomenon.