tbuckley/cabot-search huggingface dataset:
Spatial Microstimuli in Endothelial Mechanosignaling
Authors: Peter F. Davies, Jenny Zilberberg, Brian P. Helmke
Journal: Circulation Research (2003)

Descriptive and quantitative analyses of microstimuli in living endothelial cells strongly support an integrated mechanism of mechanotransduction regulated by the spatial organization of multiple structural and signaling networks. Endothelial responses to blood flow are regulated at multiple levels of organization extending over scales from vascular beds to single cells, subcellular structures, and individual molecules. Microstimuli at the cellular and subcellular levels exhibit temporal and spatial complexities that are increasingly accessible to measurement. We address the cell and subcellular physical interface between flow-related forces and biomechanical responses of the endothelial cell. Live cell imaging and computational analyses of structural dynamics, two important approaches to microstimulation at this scale, are briefly reviewed.
Effect of Testosterone Supplementation With and Without a Dual 5α-Reductase Inhibitor on Fat-Free Mass in Men With Suppressed Testosterone Production
Authors: Shalender Bhasin, Thomas G. Travison, Thomas W. Storer, Kishore Lakshman, Manas Kaushik, Norman A. Mazer, Ahn-Hoa Ngyuen, Maithili N. Davda, Hernan Jara, Adam Aakil, Stephan Anderson, Philip E. Knapp, Samson Hanka, Nurahmed Mohammed, Pierre Daou, Renee Miciek, Jagadish Ulloor, Anqi Zhang, Brad Brooks, Katie Orwoll, Leife Hede-Brierley, Richard Eder, Ayan Elmi, Geeta Bhasin, Lauren Collins, Ravinder Singh, Shehzad Basaria
Journal: JAMA (2012)

Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood.To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2).The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010.Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups).The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels.A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups.Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle.clinicaltrials.gov Identifier: NCT00493987.
The Mechanism of Bicarbonate Secretion in Rabbit Ileum Exposed to Choleragen
Authors: Kenneth A. Hubel
Journal: Journal of Clinical Investigation (1974)

BICARBONATE MAY BE SECRETED INTO THE INTESTINAL LUMEN IN CHOLERA BECAUSE: HCO(3) (-) ions are transported, or because OH(-) ions accumulate and react with dissolved CO(2) to form HCO(3) (-). If HCO(3) (-) ions are transported into the lumen from the interstitial fluid, lumenal P(CO2) should increase (HCO(3) (-) right harpoon over left harpoon OH(-) + CO(2)); if OH(-) accumulates, P(CO2) should diminish. Net movement of H(2)O, and HCO(3) (-), and changes in pH and P(CO2) in lumenal fluid were studied in adjacent segments of rabbit ileum in vivo, one of which was exposed to choleragen. 4 h after exposure, segments were drained and infused with gassed Krebs-Henseleit solution whose P(CO2) exceeded arterial P(CO2). After 45 min, fluid was collected anaerobically from control and cholera segments. Among 13 cholera segments, lumenal P(CO2) diminished by a mean of 8.4 torr and was less than femoral arterial blood in six instances. In the paired control segments, mean P(CO2) increased by 4.4 torr, and was always greater than arterial P(CO2). Dilution could not account for the low P(CO2) in cholera segments because in hypertonic solutions that caused water to move into the lumen, the P(CO2) did not differ from control values obtained with isotonic solutions. The results suggest that OH(-) accumulation (by addition of OH(-) or removal of H(+)) causes HCO(3) (-) secretion in cholera. This does not result from secretion of some other base (e.g., HPO(4) (-)), because HCO(3) (-) accounts for most of the base in the lumenal fluid. The P(CO2) changes suggest that OH(-) reacts with CO(2) at the cell-lumen interface, but reaction at the cell-interstitial fluid interface cannot be excluded.
Review of research on the mechanical properties of the human tooth
Authors: Ya-Rong Zhang, Wen Du, Xue-Dong Zhou, Hai-Yang Yu
Journal: International Journal of Oral Science (2014)

'Bronze teeth' reflect the mechanical properties of natural teeth to a certain extent. Their mechanical properties resemble those of a tough metal, and the gradient of these properties lies in the direction from outside to inside. These attributes confer human teeth with effective mastication ability. Understanding the various mechanical properties of human teeth and dental materials is the basis for the development of restorative materials. In this study, the elastic properties, dynamic mechanical properties (visco-elasticity) and fracture mechanical properties of enamel and dentin were reviewed to provide a more thorough understanding of the mechanical properties of human teeth. Understanding the mechanical properties of human teeth could enhance artificial tooth development, dental scientists in China conclude in a review of recent research. Artificial teeth are required to make incisions, lacerate and grind food like natural teeth, but the perfect material to make them remains undiscovered. This deficiency is partly because of gaps in current knowledge regarding the structural and mechanical properties of the two main dental tissues, enamel and dentin. After reviewing recent research into both tissues, Xue-Dong Zhou, Hai-Yang Yu and co-workers at Sichuan University, China, recommend further investigations — particularly at the microscopic level — into the elastic mechanics and fracture-resistant qualities of dental tissues. The team believes it is important also to investigate how these properties change as people age, and how the surrounding oral environment affects tooth strength and fracturing.
ASSOCIATION OF ALDOSTERONE SYNTHASE POLYMORPHISM (CYP11B2–344T&gt;C) WITH ATRIAL FIBRILLATION IN AFRICAN-AMERICANS WITH HEART FAILURE
Authors: Adam Phillip Bress, Shitalben Patel, Ankit A. Desai, Ibrahim Mansour, Vicki Groo, Jin Han, Kristin Progar, Ebony Shah, Thomas Stamos, Rick Kittles, Larisa Cavallari
Journal: Journal of the American College of Cardiology (2013)
Value of the Problem-Oriented Record
Authors: Burton A. Waisbren
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Recent articles in the LETTERS section regarding the problem-oriented medical record make me believe that physicians such as myself, who do not think that the problem-oriented record will survive, because it demands more writing from physicians rather than less, should know that an alternative form of record is possible. This alternative is a mission-oriented medical record (<i>Crit Care Med</i>1:261, 1973), so named because its<i>sole</i>mission is to help the doctor meet the needs of the patient in a manner amenable to automatic quality control. In this record the physician makes three lists. The first relates to the problems of the patient, the second is a list of the data pertinent to the problems, and the third consists of solutions to the problems, ie, the orders. Each list checks the accuracy of the others in that the data should explain how the problems are perceived and
Uptake of Chemically Reactive, DNA-Damaging Sulfuric Acid Esters into Renal Cells by Human Organic Anion Transporters
Authors: Nadiya Bakhiya, Monika Stephani, Andrew Bahn, Bernhard Ugele, Albrecht Seidel, Gerhard Burckhardt, Hansruedi Glatt
Journal: Journal of the American Society of Nephrology (2006)

The procarcinogen 1-methylpyrene is activated by hepatic enzymes via 1-hydroxymethylpyrene to 1-sulfooxymethylpyrene (1-SMP), a highly reactive and mutagenic metabolite. Previously, high levels of 1-SMP DNA adducts were observed in rat kidneys after intraperitoneal administration of 1-hydroxymethylpyrene or 1-SMP. This study examined whether organic anion transporters (OAT) that are expressed at the basolateral membrane of proximal tubule cells are involved in uptake of SMP. Human epithelial kidney (HEK293) cells that stably express human OAT1 (hOAT1) and hOAT3 were used. Stable isomers of 1-SMP, (2-SMP and 4-SMP) competitively inhibited the uptake of characteristic substrates p-aminohippurate for hOAT1 and estrone sulfate for hOAT3. Both inhibitors exhibited high affinity for hOAT1 (K(i) = 4.4 microM for 2-SMP; K(i) = 5.1 microM for 4-SMP) as well as hOAT3 (K(i) = 1.9 microM for 2-SMP; K(i) = 2.1 microM for 4-SMP). The uptake rate of 4-SMP (at a concentration of 10 microM) by hOAT1- and hOAT3-expressing cells was 3.0 and 1.6 times higher, respectively, than in control cells. Uptake of the reactive isomer 1-SMP was investigated using as the end point the level of DNA adducts that were formed in the cells. After exposure to 1-SMP (10 microM), the DNA adduct level was 4.6 and 3.0 times higher in hOAT1- and hOAT3-expressing cells, respectively, than in control cells. The enhanced DNA adduct formation in hOAT-expressing cells was abolished in the presence of the OAT inhibitor probenecid. This study indicates that OAT can mediate the basolateral uptake of reactive sulfuric acid esters into proximal tubule cells and thereby participate in kidney cell damage by these compounds.
HIV Testing is the Answer — What's the Question?
Authors: Robin Weiss, Samuel O. Thier
Journal: New England Journal of Medicine (1988)

There is reason for concern about the false positive rate in testing for antibody to the human immunodeficiency virus (HIV). Even when the specificity of a test is high, some persons who are truly without disease will nevertheless test positive. In populations in which the prevalence of disease is low, these false positive results represent a substantial proportion of all positive results, lowering the probability that a positive test result indicates true disease.1 , 2 The potential consequences of incorrectly informing a person that he or she is infected with HIV are severe: certainly anguish, fear, and depression; perhaps lost jobs, denied . . .
The Truth About the Drug Companies: How they deceive us and what to do about it
Authors: Fred Charatan
Journal: BMJ (2004)

D r Marcia Angell, a member of Harvard Medical School's Department of Social Medicine, has written a painstakingly researched book on the wiles and ways of what has come to be called “big pharma.” It is a clear expose of the American drug industry and is written in the impassioned but impeccable prose we expect from a former editor of the New England Journal of Medicine.    ![][1] 

Marcia Angell

Random House, $24.95, pp 336 ISBN 0 375 50846 5 Also available as an ebook, $17.95 http://www.randomhouse.com/

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Angell says that $200bn (£110bn; €165bn) is spent annually on prescription drugs in the United States. With the cost rising 12% a year, it is the fastest growing part of America's swollen health bill. In 2002 the average price of the 50 commonest drugs used by elderly people was nearly $1500 for a year's supply. At, say, six prescriptions—not an uncommon number among elderly Americans—that's $9000 a year for one person's drugs. What are the remedies for this unaffordable financial …

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Goodale's Clinical Interpretation of Laboratory Tests
Authors: Sanford A. Franzblau
Journal: JAMA (1973)

If brevity is the soul of wit, so is clarity the essence of any useful reference work for the busy clinician. The author has taken large amounts of material from the literature of clinical pathology and analyzed it thoughtfully and clearly. In carefully chosen phrases she has reassembled it in quintessential form and served it up garnished with wellplanned illustrations. The entire structure is buttressed with a good bibliography and made approachable through an adequate index. A division is made between sections devoted to laboratory principles on the one hand and clinical findings on the other, a distinction that I find unnecessary and confusing. Hemolytic diseases of the newborn are discussed under laboratory principles, while coagulopathies are discussed under clinical findings. Ignoring such divisions puts it all together, and one can then get on with the important purpose and usefulness of the book. I would recommend that the person using
Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome
Authors: T Jensen, M Klarlund, M Hansen, K E Jensen, J Pødenphant, T M Hansen, H Skjødt, L Hyldstrup
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To compare changes in regional bone mineral density (BMD) of the metacarpal joints measured by dual <i>x</i> ray absorptiometry (DXA) and digital <i>x</i> ray radiogrammetry (DXR) in relation to disease activity and radiographic outcome in a two year follow up study of patients with early RA and unclassified polyarthritis. <b>Patients and methods:</b> 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least four weeks and less than two years were included. 51 patients fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis. The patients with RA were divided into groups according to mean disease activity, average glucocorticoid dose, and MRI and <i>x</i> ray detected bone erosions in the hands. Clinical and biochemical measurements were made every month and an <i>x</i> ray examination of the hands and BMD of the metacarpal joints every six months. <b>Results:</b> DX<b>R</b> BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease. No changes in BMD measured by DX<b>A</b> were seen in any patient group. <b>Conclusion:</b> DX<b>R</b> is a useful measure of the destructive disease activity in patients with RA and unclassified polyarthritis, providing valuable information about bone changes associated with disease activity and erosive disease in early RA. DX<b>R</b> is better than DX<b>A</b> for detecting and monitoring periarticular osteoporosis of the metacarpal bone.
Measuring and Improving the Quality of Care for Abdominal Aortic Aneurysm Surgery
Authors: Justin B. Dimick, Gilbert R. Upchurch
Journal: Circulation (2008)

B ecause of widespread recognition of variations in surgi- cal performance, patients and payers are placing renewed focus on holding providers accountable for the quality of care they provide.Patients are becoming more cautious informed consumers.Payers are stepping up efforts to align reimbursement to physicians and hospitals with the quality of care they provide.Providers can count on quality measurement and improvement being part of the health policy landscape for the foreseeable future.As stakeholders in this movement, we need to continually refine and update our understanding of the best approach to answer this call for accountability, and each of us needs to fulfill our obligation to contribute to the improvement of our clinical specialty.The purpose of this article is to update our knowledge on the best methods to approach quality measurement and improvement in aortic surgery.Whereas many agree that improving the quality of care is important, few agree on the best way to go about it.The available approaches to measure the quality of care for high-risk abdominal aortic aneurysm surgery will be reviewed.In addition, the promise and pitfalls of existing improvement efforts will be considered.Abdominal aortic aneurysm repair is both a relatively common and high-risk procedure.Many patients die each year after elective repair of abdominal aortic aneurysms. 1Improving the quality of care provided to these patients could potentially avert many of these deaths.For this reason, operations for aortic aneurysm disease are often the focus of quality measurement and improvement.Although most existing quality measurement initiatives focus on a narrow group of operations, they invariably include surgery for abdominal aortic aneurysms.
Dermal Wound Healing Is Subject to Redox Control
Authors: Sashwati Roy, Savita Khanna, Kishore Nallu, Thomas K. Hunt, Chandan K. Sen
Journal: Molecular Therapy (2005)

Previously we have reported in vitro evidence suggesting that that H2O2 may support wound healing by inducing VEGF expression in human keratinocytes (C. K. Sen et al., 2002, J. Biol. Chem. 277, 33284–33290). Here, we test the significance of H2O2 in regulating wound healing in vivo. Using the Hunt–Schilling cylinder approach we present the first evidence that the wound site contains micromolar concentrations of H2O2. At the wound site, low concentrations of H2O2 supported the healing process, especially in p47phox- and MCP-1-deficient mice in which endogenous H2O2 generation is impaired. Higher doses of H2O2 adversely influenced healing. At low concentrations, H2O2 facilitated wound angiogenesis in vivo. H2O2 induced FAK phosphorylation both in wound-edge tissue in vivo and in human dermal microvascular endothelial cells. H2O2 induced site-specific (Tyr-925 and Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H2O2. Adenoviral gene delivery of catalase impaired wound angiogenesis and closure. Catalase overexpression slowed tissue remodeling as evidenced by a more incomplete narrowing of the hyperproliferative epithelium region and incomplete eschar formation. Taken together, this work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes.
Alcohol industry's response to BMJ investigation of consultation on minimum price for alcohol
Authors: M. Beale, B. Simmons, B. Price, D. Frost
Journal: BMJ (2014)

We would like to respond to several points made in the BMJ investigation of the consultation on the minimum price for alcohol.1

Firstly, the report argued that the number of meetings between government and the alcohol industry indicated unjustified access to government to lobby against minimum unit pricing. In reality, the government invited businesses to those meetings as part of the public health responsibility deal, and our representation …
Relief of Malignant External Gastric Obstruction by Endoscopic Implantation of a Self-Expanding Metal Stent
Authors: A. Sommer, N. Bethge
Journal: Endoscopy (1995)

We report on the case of a 63-year-old woman with a gastric stenosis caused by peritoneal carcinomatosis. Vomiting and nausea disappeared after the implantation of a self-expanding metal stent in the 5 cm-long stenosis, and the patient was able to maintain a normal diet. She was discharged from hospital and remained in good condition for 14 weeks. Then, 16 weeks after stent implantation, the patient died of metastatic tumor spread, having remained free of nausea and vomiting. An autopsy showed complete patency of the stent, and no signs of ulceration or tumor ingrowth. The success of the treatment in this patient suggests the importance of further investigations.
Correction in "A Few Clinical Pictures."
Authors: John A. Wessinger
Journal: JAMA (1899)

Ann Arbor, Mich., Feb. 27, 1899. <h3>To the Editor:</h3> —In my article published in theJournalof Feb. 18, 1899, (p. 360), in the report of Case No. 5 the statement is made that "she has had local medical treatment for two years with no improvement." Since writing this, the physician who treated the patient before I saw her, and who last saw her about a year before she came to me, informs me that when the patient first came under his observation she was the subject of a marked uterine subinvolution, the fundus reaching as high as the umbilicus. I know the physician to be an accurate observer, and therefore feel it just to say that so far as this condition is concerned, "the local medical treatment" had improved the patient, as involution was complete when she came to my notice. Under report of Case No. 6, in the
Immunosuppression in Organ Transplantation
Authors: Charles B. Carpenter
Journal: New England Journal of Medicine (1990)

The search for effective and safe methods of suppressing the immune response has been evolving over four decades. Progress has been marked by many disappointments and a few forward leaps. Clinical organ transplantation has served as the proving ground for many of these advances, beginning in the early 1950s, shortly after a working model of the artificial kidney provided for the short-term maintenance of life in patients with end-stage renal disease. The first attempts to suppress the rejection response, with whole-body irradiation and bone marrow transplantation, were unsuccessful. Since then, there have been two main avenues of approach to the . . .
Treatment of polycythaemia vera.
Authors: P. J. Watkins, G. H. Fairley, R. B. Scott
Journal: BMJ (1967)

MaterialPolycythaemia vera was diagnosed when the haemoglobin was greater than 17 g./100ml. or the red cell count greater than 6,000,000/cu.mm., together with one other feature-namely, a leucocyte count greater than 12,000/cu.mm., a platelet count greater than 300,000/cu.mm., or splenomegaly.Acute leukaemia was diagnosed when both blood and marrow were on 29 May