tbuckley/cabot-search huggingface dataset:
Morning increase in platelet aggregability. Association with assumption of the upright posture.
Authors: D A Brezinski, G H Tofler, J E Muller, S Pohjola-Sintonen, S N Willich, A I Schafer, C A Czeisler, G H Williams
Journal: Circulation (1988)

The frequencies of onset of myocardial infarction and sudden cardiac death are increased between 6 AM and 12 noon. Platelet aggregability, which may play a role in the cause of these disorders, has been observed to increase after the normal morning activities of awakening, arising, and ambulating. To determine which morning activity or activities are responsible for this aggregability increase, we measured platelet aggregation in 16 normal subjects on a control day of delayed arising (i.e., subjects remained supine until 12:30 PM) and on a day in which normal morning activities were divided into three isolated components of awakening (8 AM), assumption of upright posture (9:30 AM), and ambulating (11 AM). Blood samples to assess platelet aggregability were drawn at 8 AM before activity and 90 minutes after the initiation of each activity (i.e., at 9:30 AM, 11 AM, and 12:30 PM). For the group, in vitro platelet responsiveness to adenosine diphosphate and epinephrine increased only after assumption of the upright posture. The lowest concentration of agonist required to produce biphasic platelet aggregation decreased (aggregability increased) between 9:30 and 11 AM (90 minutes after assumption of the upright posture) from 3.3 +/- 0.3 to 2.4 +/- 0.2 microM for adenosine diphosphate (p less than 0.05) and from 2.1 +/- 0.5 to 1.0 +/- 0.4 microM for epinephrine (p less than 0.05). During the same interval, plasma epinephrine increased from 34 +/- 7 to 55 +/- 9 pg/ml (p less than 0.05), and plasma norepinephrine increased from 169 +/- 19 to 298 +/- 25 pg/ml (p less than 0.01). There was no significant change in aggregability or catecholamine concentrations on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)
Response to Cooling Temperature in Infants Born at an Altitude of 4,330 Meters
Authors: PETER B. FRAPPELL, FABIOLA LEÓN-VELARDE, LOURDES AGUERO, JACOPO P. MORTOLA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The metabolic response to reduction in ambient temperature was studied in healthy, full-term, 1-d-old infants in Lima (50 m altitude, n = 20) and Cerro de Pasco (4,330 m, barometric pressure ∼ 450 mm Hg, n = 20), Peru. Oxygen consumption (V˙ o 2) and carbon dioxide production (V˙ co 2) were measured with an open-flow system as each infant rested quietly in a cylindrical humicrib, at wall temperatures of 35 ° C (warm) and 26 ° C (cool). The infants were exposed for 20 min to both temperatures, with the higher temperature followed by the lower, and oxygen consumption (V˙ o 2) and carbon dioxide production (V˙ co 2) were measured over the last 8 min of each exposure. Average birth weight in Cerro de Pasco (2,933 ± 77 g [mean ± SE]) was less than in Lima (3,457 ± 73 g). In warm conditions, infants born at high altitude had slightly yet significantly lower body and skin temperatures than did those born at low altitude, with similar values of V˙ o 2 and heart rate (HR). Neither body nor skin temperature changed in either group during cooling. At low altitude, cooling increased V˙ o 2 ( ∼ 34%), whereas no significant increase occurred in the high-altitude group. A similar response occurred for HR. Among several possibilities, the most likely interpretation of the results would be that of a decreased thermogenic capacity in the high-altitude infants because of the correspondingly lower oxygen availability during gestation.
Top tips for social media use in sports and exercise medicine: doing the right thing in the digital age
Authors: Osman Hassan Ahmed, Richard Weiler, Anthony G Schneiders, Paul McCrory, S John Sullivan
Journal: British Journal of Sports Medicine (2015)

Sports and exercise (SEM) clinicians need thick skin and a nimble brain to juggle the plethora of competing professional responsibilities; from athlete clinical care, to work/life pressures, all while developing professional knowledge and skills. In recent years there has also been an assertion that SEM clinicians need to develop/maintain a social media presence, and many working in amateur and elite sport now have Facebook, Twitter and Instagram profiles. Although professional bodies have provided social media guidance (see web appendix for additional reading) there is no explicit SEM specific social media guidance.

In amateur sport, where there is not the day-to-day contact with athletes that a professional sporting environment allows, social media represents a channel of communication between the sports clinician and the athlete.1 ,2 In this hyperconnected age it is appropriate to interact with the athletes under our care using social media, but this needs to be carried out in a way that is professional, ethical and in keeping with the social media guidance from the respective professional organsations (see web appendix). Private discussions using social networks can help resolve communication/geographical challenges and may include multiple members of the multidisciplinary team at once, which can be beneficial while simultaneously remaining confidential (eg, WhatsApp messages …
Proteasome inhibition potentiates CYP2E1-mediated toxicity in HepG2 cells
Authors: María José Pérez, Arthur I. Cederbaum
Journal: Hepatology (2003)

Chronic ethanol consumption causes increased oxidative damage in the liver. Induction of CYP2E1 is one pathway involved in how ethanol produces oxidative stress. Ethanol can cause protein accumulation, decreased proteolysis, and decreased proteasome activity. The objective of this study was to investigate the effect of inhibition of the proteasome activity on CYP2E1–dependent toxicity. HepG2 cells over–expressing CYP2E1 (E47 cells) were treated with arachidonic acid (AA) plus iron, agents important in development of alcoholic liver injury and which are toxic to E47 cells by a mechanism dependent on CYP2E1, oxidative stress, and lipid peroxidation. Addition of various proteasome inhibitors was associated with significant potentiation of the loss of cell viability caused by AA plus iron. Potentiation of toxicity was associated with increased oxidative damage as reflected by an increase in lipid peroxidation and accumulation of oxidized and nitrated proteins in E47 cells and an enhanced decline in mitochondrial membrane potential. Antioxidants prevented the loss of viability and the potentiation of this loss of viability by proteasome inhibition. CYP2E1 levels were elevated about 3–fold by the proteasome inhibitors. Inhibition of proteasome activity also potentiated toxicity of AA alone and toxicity after treatment to remove glutathione (GSH). Similar results were found in hepatocytes from pyrazole–treated rats with high levels of CYP2E1. In conclusion, proteasome activity plays an important role in modulating CYP2E1–mediated toxicity in HepG2 cells by regulating CYP2E1 levels and by removal of oxidized proteins. Such interactions may be important in CYP2E1–catalyzed toxicity of hepatotoxins and in alcohol–induced liver injury.
Toxicity of Combined Ganciclovir and Zidovudine for Cytomegalovirus Disease Associated with AIDS
Authors: H Hochster, D Dieterich, S Bozzette, R C Reichman, J D Connor, L Liebes, R L Sonke, S A Spector, F Valentine, C Pettinelli
Journal: Annals of Internal Medicine (1990)

To assess the toxicity, efficacy, and pharmacology of combined zidovudine and ganciclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS) and serious cytomegalovirus (CMV) disease.Prospective, phase I multicenter trial (ACTG 004) with patients grouped by previous study drug history.Three university-based AIDS Clinical Trials Units sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).Forty-one patients with AIDS-related CMV disease. Previous therapy with either zidovudine or ganciclovir was allowed.Patients were treated with zidovudine, 600 to 1200 mg/d; or, if on ganciclovir maintenance, ganciclovir, 5 mg/kg body weight; blood was sampled for pharmacokinetic studies. The other drug was then administered to the patient with blood sampling and, finally, the two drugs in combination were given. Patients were continued on both drug therapies with dose reduction of zidovudine only for grade 3 or 4 toxicity.Forty patients were eligible. Hematologic toxicity was frequent, with 9 of the 10 patients requiring dose reductions for grade 3 or 4 toxicity at zidovudine doses of 1200 mg/d. With zidovudine doses of 600 mg/d, 82% experienced such hematologic toxicity. Median survival was 6 months; 10 patients developed intercurrent infection and 19, progressive CMV disease. Pharmacokinetic variables (alpha and beta half-lives, volume of distribution, clearance) were not affected in combination therapy.The combination of zidovudine and ganciclovir is poorly tolerated in patients with AIDS and serious-CMV disease, with 82% developing severe to life-threatening hematologic toxicity. Such toxicity is not a result of pharmacologic interactions, drug metabolism, or excretion.
Orotate Phosphoribosyltransferase Gene Polymorphism Predicts Toxicity in Patients Treated with Bolus 5-Fluorouracil Regimen
Authors: Wataru Ichikawa, Takehiro Takahashi, Kenichi Suto, Yasutsuna Sasaki, Renzo Hirayama
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We investigated whether the determination of orotate phosphoribosyltransferase (OPRT) and thymidylate synthase (TYMS) polymorphisms could predict the toxicity of 5-fluorouracil (5-FU) in colorectal cancer patients. Experimental Design: The determination of OPRT and TYMS genotypes were done in genomic DNA extracted from blood by PCR amplification in 69 patients treated with bolus 5-FU as adjuvant chemotherapy. Associations between these polymorphisms and toxicity were evaluated retrospectively. Results: The Ala allele in OPRT Gly213Ala polymorphism and the two tandem repeats (2R) in TYMS promoter polymorphism were associated with grade 3 to 4 neutropenia and diarrhea. The multivariate logistic regression models revealed that only TYMS promoter polymorphism had an independent value to predict grade 3 to 4 neutropenia [odds ratio, 19.2 for patients with the 2R allele compared with patients with homozygous with the three repeat (3R) alleles], whereas both OPRT and TYMS promoter polymorphisms were independent predictive factors for grade 3 to 4 diarrhea (odds ratio, 13.3 for patients with the Ala allele compared with patients in the Gly/Gly genotype and 11.1 for patients with the 2R allele compared with patients in the 3R/3R genotype). A significant difference was observed in the time to onset of severe toxicity, defined as grade 4 neutropenia and/or grade 3 to 4 gastrointestinal toxicities according to OPRT and TYMS promoter polymorphisms. Conclusion: OPRT Gly213Ala polymorphism seems to be a useful marker for predicting toxicity to bolus 5-FU chemotherapy. Prospective translational treatment trials including larger number of patients are needed to confirm our results.
Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression
Authors: Eugene Tkachenko, Renee Rawson, Elizabeth La, Taylor A. Doherty, Rachel Baum, Kellen Cavagnero, Atsushi Miyanohara, Ranjan Dohil, Richard C. Kurten, Seema S. Aceves
Journal: Journal of Allergy and Clinical Immunology (2015)
Cortisol Inhibits Acid-Induced Bone Resorption In Vitro
Authors: Nancy S. Krieger, Kevin K. Frick, David A. Bushinsky
Journal: Journal of the American Society of Nephrology (2002)

Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro, metabolic acidosis has been shown to initially induce physicochemical mineral dissolution and then enhance cell-mediated bone resorption. Acidic medium stimulates osteoblastic prostaglandin E(2) production, which mediates the subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also known to decrease bone mineral density, and metabolic acidosis has been shown to increase glucocorticoid production. This study tested the hypothesis that glucocorticoids would exacerbate acid-induced net calcium efflux from bone. Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 +/- 0.01; [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] = 26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic beta-glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE(2), and osteoclast activity; Acid led to an increase in all three parameters. The addition of Cort to Acid led to a reduction of calcium efflux, medium PGE(2) levels and beta-glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE(2) concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE(2) concentration and beta-glucuronidase activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid-induced, cell-mediated osteoclastic bone resorption through a decrease in osteoblastic PGE(2) production. These results suggest that the osteopenia observed in response to metabolic acidosis in vivo is not due to an increase in endogenous cortisol production.
Clearnace of Fe59-labelled erythrocytes from normal and inflamed rabbit knee joints. I. Relationship to the anaemia of rheumatoid arthritis.
Authors: K D Muirden
Journal: Annals of the Rheumatic Diseases (1969)

The anaemia of rheumatoid arthritis has features suggestive of iron deficiency even in the absence of occult blood loss (Jeffrey, 1965).There is some evidence that this may be due to reduced availability of iron from storage sites in the reticulo-endothelial system (Weinstein, 1959; Owen and Lawson, 1966).Extensive deposits of iron are frequently found in the synovial membrane in this disease and these have recently been considered as a further important storage site for iron (Muirden and Senator, 1968; Mowat and Hothersall, 1968).Sequestration of iron in the synovium could contribute to the hypo- ferraemia and anaemia of this condition.To test this hypothesis a study was made of the clearance of Fe59 labelled to red blood cells from inflamed and normal knee joints of rabbits.The radiation was measured by surface counting and by liquid scintillation of ashed segments of tissue.The eventual distribution of iron in the joint was measured histochemically and by autoradiography and these results will be described in a subsequent paper. Material and MethodsCarragheenin arthritis was induced in the right knee joints of rabbits by the method of Gardner (1960).Eight to ten injections of 0 8 ml. of a 1 per cent.solution were given over a period of 5 to 6 weeks.This is known to produce a chronic inflammation which will persist for at least 5 weeks without additional stimulus before beginning to subside.The left knee joint was given an equal quantity of normal saline at the same time.Fe69 labelled red cells were prepared by intravenous injections of Fe69 citrate into a further rabbit.Approximately 150 JLc. were required to produce a peripheral blood radioactivity of 1 to 2 /Lc./ml.after 2 to 3 weeks.
A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors
Authors: A.W. Tolcher, J.C. Bendell, K.P. Papadopoulos, H.A. Burris, A. Patnaik, S.F. Jones, D. Rasco, D.S. Cox, M. Durante, K.M. Bellew, J. Park, N.T. Le, J.R. Infante
Journal: Annals of Oncology (2014)
Mark Twain and Medicine: Any Mummery Will Cure
Authors: William H. Kober
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes19 October 2004Mark Twain and Medicine: Any Mummery Will CureWilliam H. Kober, MDWilliam H. Kober, MDFrom North Adams, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-8-200410190-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Ober P. 384 pages. Columbia, MO: Univ of Missouri Pr; 2003. $47.50. ISBN: 0826215025. Order at www.umsystem.edu/upress.Field of medicine: Literature and medicine, American medical history, history of alternative and complementary medicine, neurasthenia, and chronic fatigue syndrome.Format: Hardcover book.Audience: Medical historians; Twain scholars; the general reader with interest in Mark Twain, 19th-century medical beliefs, and rediscovered principles and manners of patient care.Purpose: The author attempts to explain “the medical events and beliefs that affected Samuel Clemens' personal behavior and Mark Twain's writing”; to share “witty and perceptive … medical observations from one of history's most brilliant writers”; ... Author, Article, and Disclosure InformationAffiliations: From North Adams, Massachusetts. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 October 2004Volume 141, Issue 8Page: 652KeywordsChronic fatigue syndromeComplementary and alternative medicineHistory of medicineHomeopathyMeaslesNative American peopleOsteopathyPatientsScarlet feverSoftware tools ePublished: 19 October 2004 Issue Published: 19 October 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure
Authors: Barry M. Massie, Joseph F. Collins, Susan E. Ammon, Paul W. Armstrong, John G.F. Cleland, Michael Ezekowitz, Syed M. Jafri, William F. Krol, Christopher M. O'Connor, Kevin A. Schulman, Koon Teo, Stuart R. Warren
Journal: Circulation (2009)

Background— Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm. Methods and Results— This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P =0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P =0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P =0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively ( P =0.02 for warfarin versus aspirin). Conclusion— The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.
Vascular Calcifications
Authors: Jorge B Cannata-Andía, Minerva Rodríguez-García, Natalia Carrillo-López, Manuel Naves-Díaz, Bernardino Díaz-López
Journal: Journal of the American Society of Nephrology (2006)

The predisposition to vascular calcifications in patients with chronic kidney disease (CKD) has gained great interest in recent years as many studies have described its likely impact on morbidity and mortality. The mechanism by which the process of vascular calcification is produced is complex, and it does not consist in a simple precipitation of calcium and phosphate but is instead an active and modifiable process. Several "modifiable and nonmodifiable" factors that are able to promote vascular calcification are extremely frequent in patients with CKD. Most of the present strategies to decrease vascular calcifications are based in the control of the more prevalent modifiable risk factors. Unfortunately, the extremely important nonmodifiable risk factors, which are highly prevalent, such as older age, time on dialysis, and diabetes, are not under one's control. Recent studies also have shown that vascular calcifications in some localizations were associated with increased osteoporotic fractures not only in dialysis patients but also in the general population, and interestingly, mortality also was associated significantly and positively with vascular calcifications and nontraumatic bone fractures. Despite that new strategies may improve the management of vascular diseases and specifically have a positive impact on the high prevalence of vascular calcifications, still the best possible control of the bone metabolic and inflammatory parameters are in the primary line. The horizon of the coming decade looks promising, but solid clinical and epidemiologic data are needed to manage better the bone- and cardiovascular-related disorders in patients with CKD.
Cetuximab: a new hope for advanced NSCLC
Authors: S Karmali
Journal: Thorax (2009)

Advanced (stage IIIb/IV) non-small cell lung cancers (NSCLCs) are associated with poor survival on current chemotherapy regimes. Epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors are second-line treatment options. This is the first study to investigate a monoclonal antibody against the EGFR cetuximab as a potential first-line treatment option.

In this multinational open-label study across …
Solitary rheumatoid nodule of the pleura and rheumatoid pleural effusion
Authors: A Tserkezoglou, S Metakidis, H Papastamatiou-Tsimara, M Zoitopoulos
Journal: Thorax (1978)

<b>Tserkezoglou, A, Metakidis, S, Papastamatiou-Tsimara, H, and Zoitopoulos, M (1978),</b><i>Thorax,</i><b>33,</b> 769-772. <b>Solitary rheumatoid nodule of the pleura and rheumatoid pleural effusion.</b> Pleuropulmonary rheumatoid nodules are rare. We report a case of solitary rheumatoid nodule of the pleura with cavitation and coexisting pleural effusion in a young woman.