tbuckley/cabot-search huggingface dataset:
Investigation of colorectal cancer by minimal preparation CT in the frail and elderly patient
Authors: J. Saunders, C. Bowman, P. Panto, A. Menon
Journal: Gut (2011)

<h3>Introduction</h3> Frail &amp; elderly patients frequently struggle with invasive colonic investigations and cathartic bowel preparation, commonly resulting in incomplete studies of uncertain significance. It is important there is a pragmatic method of investigation for clinically significant Colorectal Cancer (CRC) in this increasing patient group, with a higher prevalence of disease. Minimal preparation CT (MPCT) provides clinicians with a reliable, well tolerated alternative to invasive investigation. It requires patients to drink oral contrast medium for 48 h before investigation without bowel preparation with a single scan in the supine position without colonic insufflation. This study aimed to assess the accuracy of MPCT in the detection of CRC in this population and its feasibility for use as a routine investigation for the frail and elderly. <h3>Methods</h3> A retrospective analysis of all 207 patients who underwent MPCT to investigate for CRC at a large district general hospital between November 2005 and October 2009. MPCT results were measured against patient outcomes, with a minimum of one year follow-up. <h3>Results</h3> There were 11 CRC in this cohort with a disease prevalence of 5.3%. MPCT correctly identified all of these lesions, with a sensitivity of 100% and negative predictive value of 100%. MPCT raised the suspicion of CRC in 29 patients that were later shown to be benign, resulting in a specificity of 84% and a positive predictive value of 27.5. Diagnostic accuracy of suspicious findings was affected by the confidence of radiological interpretation; scans with ‘possible’ rather than ‘likely’ findings made up the majority of the falsely suspicious MPCT results. There was one examination failure where the patient did not drink the oral contrast provided. <h3>Conclusion</h3> The sensitivity of MPCT in this series compares favourably to colonoscopy, which is frequently compromised by poor views or incomplete intubation in this population. MPCT was well tolerated, and so retains a significant advantage over CT colography which requires full bowel preparation and rectal insufflation. Of the 29 (14%) ‘false positive’ MPCTs, 24 (82%) had an abnormal colon at the suspicious site. Diverticular disease of the recto-sigmoid colon was the most common cause for error, which was easily characterised by flexible sigmoidoscopy. In frail patients unable to withstand routine bowel preparation or colonoscopy, MPCT is an effective and reliable investigation, and can be routinely used for the exclusion clinically relevant CRC.
Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma
Authors: Tina Cascone, Matthew H. Herynk, Li Xu, Zhiqiang Du, Humam Kadara, Monique B. Nilsson, Carol J. Oborn, Yun-Yong Park, Baruch Erez, Jörg J. Jacoby, Ju-Seog Lee, Heather Y. Lin, Fortunato Ciardiello, Roy S. Herbst, Robert R. Langley, John V. Heymach
Journal: Journal of Clinical Investigation (2011)

Angiogenesis is critical for tumor growth and metastasis, and several inhibitors of angiogenesis are currently in clinical use for the treatment of cancer. However, not all patients benefit from antiangiogenic therapy, and those tumors that initially respond to treatment ultimately become resistant. The mechanisms underlying this, and the relative contributions of tumor cells and stroma to resistance, are not completely understood. Here, using species-specific profiling of mouse xenograft models of human lung adenocarcinoma, we have shown that gene expression changes associated with acquired resistance to the VEGF inhibitor bevacizumab occurred predominantly in stromal and not tumor cells. In particular, components of the EGFR and FGFR pathways were upregulated in stroma, but not in tumor cells. Increased activated EGFR was detected on pericytes of xenografts that acquired resistance and on endothelium of tumors with relative primary resistance. Acquired resistance was associated with a pattern of pericyte-covered, normalized revascularization, whereas tortuous, uncovered vessels were observed in relative primary resistance. Importantly, dual targeting of the VEGF and EGFR pathways reduced pericyte coverage and increased progression-free survival. These findings demonstrated that alterations in tumor stromal pathways, including the EGFR and FGFR pathways, are associated with, and may contribute to, resistance to VEGF inhibitors and that targeting these pathways may improve therapeutic efficacy. Understanding stromal signaling may be critical for developing biomarkers for angiogenesis inhibitors and improving combination regimens.
Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man
Authors: Pete A. Poole, William C. Duane
Journal: Hepatology (1988)

In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14 CO 2 from [26- 14 C]Cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p &lt; 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p &lt; 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14 CO 2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man. Moreover, because this method of measuring synthesis does not require subtraction of large amounts of exogenous bile acid, these data also demonstrate more clearly than ever before that chenodeoxycholic acid causes inhibition of total bile acid synthesis while ursodeoxycholic acid causes either no change or a slight increase in synthesis.
The metabolism of fibroblasts from normal and fibrotic skin is inhibited by minoxidil in vitro
Authors: G.C. PRIESTLEY, RUTH LORD, P. STAVROPOULOS
Journal: British Journal of Dermatology (1991)

The effects of minoxidil in vitro were studied using fibroblasts grown from the lesional skin of patients with lichen sclerosus et atrophicus, morphoea and from the skin of normal individuals. The proliferation of all fibroblast lines over 3 days was inhibited in proportion to the concentration of minoxidil, being 20% or less of controls at 1 mM, where cell viability was only marginally reduced (84 +/- 2% vs. 88 +/- 2% (SEM) in controls). At 5 mM there was usually a net loss of cells and only 72% of those remaining were viable. In contrast, minoxidil at 0.1-1 mM stimulated the proliferation of foreskin keratinocytes by up to 130%. Contraction of collagen lattices containing the three types of fibroblasts was inhibited by 22-26% with 1 mM minoxidil after 5 days and by 50-94% with 5 mM. Secretion of glycosaminoglycans by normal fibroblasts showed concentration-dependent reduction, being 25 +/- 6% of that of untreated cultures with 1 mM minoxidil. These findings show that minoxidil has a range of inhibitory effects on both normal and abnormal skin fibroblasts in vitro, which contrast with its stimulation of skin epithelial cells, and support suggestions that it may provide a useful topical treatment for keloids and other fibroses.
Outcomes studies of drug induced ulcer complications: do we need them and how should they be done?
Authors: C J Hawkey
Journal: BMJ (2000)

The hazards of non-steroidal anti-inflammatory drugs are considerable, and they result in the death of up to 2000 patients a year in the United Kingdom.1 2 Protective strategies that use the prostaglandin analogue misoprostol3–7 or proton pump inhibitors8 9 have been developed by using endoscopic evaluation. These strategies have been shown to reduce the incidence of clinically important events such as ulcer bleeding.10 11 The structure of primary care in the United Kingdom lends itself to such studies

Non-steroidal anti-inflammatories exert their therapeutic and toxic effects mainly by inhibiting the cyclo-oxygenase enzyme, which is involved in prostaglandin synthesis. There are two isoforms of cyclo-oxygenase: the constitutive cyclo-oxygenase-1 is principally responsible for mucosal protection and the inducible cyclo-oxygenase COX-2 principally contributes to disease.12 13 The recent discovery of these two forms has stimulated development of selective inhibitors of cyclo-oxygenase-2,14 of which rofecoxib and celecoxib are available for clinical use.15 16 Unlike standard non-steroidal anti-inflammatories, these selective drugs do not affect gastric mucosal prostaglandins17 and do not injure the stomach at clinical doses.18 19

#### Summary points

Long term use of non-steroidal anti-inflammatory drugs can cause stomach ulcers

Selective cyclo-oxygenase-2 inhibitors reduce the risk of ulcers

Most studies have been based on endoscopic findings rather than clinical outcomes

Outcome studies need to be large, and problems exist in evaluating clinical outcomes

Future studies need to have improved outcome definitions or could be conducted in primary care groups

Regulatory authorities have been reluctant to remove warnings about ulcer complications from patient labels even though endoscopic studies show no …
Are inactivation procedures for blood products good or bad?
Authors: G. Caspari
Journal: BMJ (2002)

EDITOR—In their report on recent developments in transfusion medicine, Regan and Taylor mention that, in future, infectious diseases transmitted by cellular blood products might be prevented by inactivation procedures.1 All pathogen inactivation procedures for cellular blood products involve one step, and failure cannot be compensated by a second step.

Owing to technical constraints, validation of procedures is limited to five to seven logs. Without screening (or a virus carrier escaping the screening process), however, a platelet concentrate from a …
Peace through health
Authors: A. Vass
Journal: BMJ (2001)

By 2020 the World Health Organization and the World Bank predict that war will be one of the top 10 causes of disability and death.1 Recent events may well bring this date forward. “Is there anything that health professionals can do to prevent this?” was the key question addressed at the first international “Peace through Health” conference held last month at McMaster University (http://www.humanities.mcmaster.ca/peace-health).

Health professionals care for those wounded in war. The Red Cross was founded in 1864 specifically for this purpose. Other health agencies, such as the Nobel Prize winning Medecins Sans Frontieres, have been involved in dealing not just with the immediate but also the long term consequences of war. The cost of war goes beyond the direct health effects of bombs and bullets. Economic and social systems are disrupted, famine and epidemics may follow, and resources are …
Tetrahydrobiopterin and Dysfunction of Endothelial Nitric Oxide Synthase in Coronary Arteries
Authors: Francesco Cosentino, Zvonimir S. Katusic
Journal: Circulation (1995)

Background The l -arginine/nitric oxide pathway plays a key role in the regulation of arterial tone. Biosynthesis of nitric oxide requires activation of nitric oxide synthase in the presence of tetrahydrobiopterin as a cofactor. Biochemical studies demonstrated that activation of purified nitric oxide synthase at suboptimal concentrations of tetrahydrobiopterin leads to production of hydrogen peroxide. The present experiments were designed to determine whether in coronary arteries inhibition of tetrahydrobiopterin synthesis may favor nitric oxide synthase–catalyzed production of hydrogen peroxide. Methods and Results Primary branches of canine left anterior descending artery were incubated for 6 hours in minimum essential medium in the presence or in the absence of the tetrahydrobiopterin synthesis inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP; 10 −2 mol/L). Arterial rings were suspended for isometric tension recording. Production of cGMP was measured by radioimmunoassay. Experiments were performed in the presence of indomethacin (10 −5 mol/L). During contractions to the thromboxane A 2 /prostaglandin H 2 receptor agonist U46619 (10 −7 mol/L), calcium ionophore A23187 (10 −9 to 10 −6 mol/L) caused endothelium-dependent relaxations. A nitric oxide synthase inhibitor, N G -nitro- l -arginine methyl ester (3×10 −4 mol/L), significantly inhibited these relaxations. In DAHP-treated arteries, relaxations to A23187 and its stimulating effect on cGMP production were significantly reduced in the presence of catalase (1200 U/mL). By contrast, catalase did not exert any effect in rings incubated in the absence of DAHP. Furthermore, the inhibitory effect of catalase on A23187-induced relaxations was abolished when coronary arteries were incubated in the presence of DAHP plus a liposoluble analogue of tetrahydrobiopterin, 6-methyltetrahydropterin (10 −4 mol/L). Conclusions The present study suggests that hydrogen peroxide may be a mediator of endothelium-dependent relaxations in coronary arteries depleted of tetrahydrobiopterin. This initially compensatory response, triggered by a dysfunctional nitric oxide synthase, may represent an important mechanism underlying oxidative vascular injury.
Oxygen Tents vs. Air Conditioners
Authors: Leon J. Warshaw
Journal: JAMA (1961)

<h3>To the Editor:—</h3> An editorial in the June 24 issue ofThe Journaloffers a timely reminder of the deleterious effects of hot and humid weather, and closes by suggesting the oxygen tent as a "simple, inexpensive and readily available" method for providing relief for a hospitalized patient whose room is not air conditioned. Unquestionably, oxygen tents can be used for this purpose. However, caring for a patient in an oxygen tent means more work for hospital personnel. The tents are costly to purchase and to operate. In view of the limited numbers usually available, using them to provide air conditioning may mean the lack of a tent for a patient who needs one for oxygen therapy. Modern air conditioner units are easily installed and, as a rule, place no greater load on a hospital's power supply or electrical wiring. They are more readily available, much more convenient to use,
Use of antipsychotic drugs was associated with increased risk for hyperglycemia in older patients with diabetes
Authors: Bradley Ng
Journal: Annals of Internal Medicine (2009)

ACP Journal Club17 November 2009Use of antipsychotic drugs was associated with increased risk for hyperglycemia in older patients with diabetesBradley Ng, MBChB, FRANZCPBradley Ng, MBChB, FRANZCPRobina Hospital, Gold Coast, Queensland, Australia (B.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-10-200911170-02012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLipscombe LL, Lévesque L, Gruneir A, et al. Antipsychotic drugs and hyperglycemia in older patients with diabetes. Arch Intern Med. 2009;169:1282−9. https://pubmed.ncbi.nlm.nih.gov/19636029Clinical Impact RatingsGIM/FP/GP: Mental Health: Hospitalists: Endocrinology: Geriatrics: Author, Article, and Disclosure InformationAffiliations: Robina Hospital, Gold Coast, Queensland, Australia (B.N.)This article was published at Annals.org on 3 November 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 November 2009Volume 151, Issue 10Page: JC5-12KeywordsAntipsychoticsEmergency departmentHospitalizationsHyperglycemiaInsulinLong-term careMedical dialysisNumber needed to harmPalliative carePsychiatry and mental health ePublished: 17 November 2009 Issue Published: 17 November 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of Trimethoprim-sulphamethoxazole on Typhoid and Salmonella Carriers
Authors: J. Brodie, I. A. Macqueen, D. Livingstone
Journal: BMJ (1970)

Four chronic typhoid carriers from the Aberdeen typhoid outbreak of 1964 were treated with trimethoprim-sulphamethoxazole. The male carrier remained clear of infection following treatment but the three female carriers, all with gall bladder abnormalities, remained excretors. A convalescent typhoid excretor also remained clear of infection after treatment as well as two other salmonella carriers, one of whom has been a chronic carrier for 24 years.
Psychiatric Peer Review: Prelude and Promise
Authors: Lionelle D. Wells
Journal: JAMA (1987)

John Hamilton, as editor of this book, has compiled an interesting and informative history of the American Psychiatric Association's (APA) endeavors to develop psychiatric peer review. Much of the work was done with the Civilian Health and Medical Program for the Uniformed Services (CHAMPUS), and the story of the relationship between the APA and CHAMPUS is worthwhile to understand the fusion of a professional society whose primary purpose is to ensure quality of care and a third-party payer whose primary purpose is to control costs of care. This book demonstrates that both goals can be achieved through a trust and respect for each other. So many psychiatrists are suspicious of the motives of third-party payers and are afraid of peer review being abused by third-party payers. This book largely answers these concerns and goes a long way toward reassuring the psychiatrist that peer review is an educational learning experience for
telederm.org: Freely Available Online Consultations in Dermatology
Authors: H. Peter Soyer, Rainer Hofmann-Wellenhof, Cesare Massone, Gerald Gabler, Huiting Dong, Fezal Ozdemir, Giuseppe Argenziano
Journal: PLoS Medicine (2005)

“e-Health matters. It can improve access to healthcare and boost the quality and effectiveness of the service offered. e-Health describes the application of information and communications technologies across the whole range of functions that affect the health sector.” This is the introductory statement of a recent communication from the European Commission that produced the report “e-Health—Making Healthcare Better for European Citizens: An Action Plan for a European e-Health Area” [1]. Easy access to expert medical information and counseling independent of social, economic, ethnic, and regional factors is regarded as a major goal of medical policy today. The visual nature of dermatology makes this discipline an obvious candidate for telemedicine techniques, and the feasibility and reliability of teledermatology is already well-established [2,3]. In recent years the teledermatology group of the Department of Dermatology at the Medical University of Graz, Austria, has been involved in several national and international teledermatology projects, with particular emphasis on clinical dermatology, clinicopathologic correlation, and evaluation of pigmented skin lesions [4,5]. Among the activities of the teledermatology group was the organization of the Third European Symposium on Teledermatology in Graz in November 2002 (http://telederm.uni-graz.at). Furthermore, together with colleagues from the Department of Dermatology in Jena, Germany, the Graz teledermatology group founded the International Society of Teledermatology (http://www.teledermatology-society.org), whose goal is to promote the worldwide exchange of knowledge and expertise in all aspects of dermatology.
In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts.
Authors: Y Takeishi, G Chu, D M Kirkpatrick, Z Li, H Wakasaki, E G Kranias, G L King, R A Walsh
Journal: Journal of Clinical Investigation (1998)

Recently, it has been reported that the protein kinase C (PKC) beta isoform plays a critical role in the development of hypertrophy and heart failure. The purpose of the present study was to clarify the mechanism by which activation of PKCbeta led to depressed cardiac function. Thus, we used a PKCbeta2 overexpressing mouse, an animal model of heart failure, to examine mechanical properties and Ca2+ signals of isolated left ventricular cardiomyocytes. The percentage of shortening, rate of shortening, and rate of relengthening of cardiomyocytes were markedly reduced in PKCbeta2 overexpression mice compared to wild-type control mice, although the baseline level and amplitude of Ca2+ signals were similar. These findings suggested a decreased myofilament responsiveness to Ca2+ in transgenic hearts. Therefore, the incorporation of [32P] inorganic phosphate into cardiac myofibrillar proteins was studied in Langendorff-perfused hearts. There was a significant increase in the degree of phosphorylation of troponin I in PKCbeta2-overexpressing transgenic mice. The depressed cardiomyocyte function improved after the superfusion of a PKCbeta selective inhibitor. These findings indicate that in vivo PKCbeta2-mediated phosphorylation of troponin I may decrease myofilament Ca2+ responsiveness, and thus causes cardiomyocyte dysfunction. Since chronic and excess activation of PKCbeta2 plays a direct and contributory role in the progression of cardiac dysfunction, the PKCbeta selective inhibitor may provide a new therapeutic modality in the setting of heart failure.
Neuritogenic Surfaces using Natural Product Analogs
Authors: Patrick Burch, Fabian Schmid, Karl Gademann
Journal: Advanced Healthcare Materials (2014)

Neuritogenic surfaces are generated by a simple dip-coating procedure, as glass slides are coated with a neurotrophin-like small organic molecule in the presence of a collagen matrix. The surfaces retain their biological activity for multiple cycles and the protocol is suitable for various substrates and coating conditions. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.