tbuckley/cabot-search huggingface dataset:
The effects of posture and isoproterenol on the velocity of left ventricular contraction in man
Authors: H. W. Paley, Ian G. McDonald, Joseph Blumenthal, James Mailhot, Gunnard W. Modin
Journal: Journal of Clinical Investigation (1971)

A study was performed in five normal men in whom left ventricular volume was measured by thermodilution in the supine and 60 degrees head-up postures, in the control state, and then during steady-state response to isoproterenol. The mean rate of circumferential shortening of the left ventricle was calculated for each of the postures in both inotropic states and was found to remain constant in the control state at 12.5 +/-0.6 cm/sec in the supine posture and 13.3 +/-0.5 cm/sec in the tilted posture. Similarly, mean rate of circumferential shortening remained constant in response to the positive inotropic effect of isoproterenol at 20.9 +/-0.5 cm/sec in the supine position and 20.7 +/-0.5 cm/sec in the tilted posture. It is concluded that the constancy of mean rate of circumferential shortening over the relatively broad physiologic range of left ventricular end-diastolic volume and mean force of ejection during a given state of myocardial contractility represents the coupled reciprocal influences of ventricular wall tension and myocardial fiber length on the velocity of ventricular wall shortening. Unlike stroke work, stroke power, and mean rate of left ventricular ejection, which are volume-dependent parameters of myocardial performance, the mean rate of circumferential shortening appears to be a reasonable index of left ventricular contractility, which in steady-state conditions is independent of left ventricular end-diastolic volume and mean ventricular wall force of ejection. In this study, changes in mean rate of circumferential shortening associated with changes of heart rate were small and variable.
Kitemarking the west wind
Authors: G. Eysenbach
Journal: BMJ (2001)

# Website labels are analogous to food labels {#article-title-2}

EDITOR—We disagree with several of the ideas expressed by Delamothe in his editorial—for example, that we cope without the help of kitemarks and gateways in the real world. 1 2 Book reviews, television programmes, even the BMJ are all counterparts of “infomediaries.” There is also consensus that any gateway, kitemark, or trustmark cannot and does not intend to guarantee the “accuracy” or completeness of information,3 as implied by the editorial. Instead, they should be seen and used as tools to increase transparency.

The European Union project MedCERTAIN (MedPICS Certification and Rating of Trustworthy and Assessed Health Information on the Net) will use the concept of a third generation of trustmark, which must be discriminated from traditional kitemarks. The approach can best be explained by drawing an analogy to food labels. In order to direct consumers to a healthy diet we are not telling them which products to eat specifically; instead we educate consumers about healthy constituents of …
SAR and chemistry of Aurora kinase inhibitors: Discovery of PF-3814735, an oral clinical candidate
Authors: Samit Bhattacharya, Donn Wishka, Michael Luzzio, Joel Arcari, Vincent Bernardo, David Briere, Tracy Boyden, Mary Campbell, Bruce Cohen, Kevin Coleman, Erling Emerson, John Jakubczak, Jitesh Jani, Chao Li, Matthew Marx, James Moyer, Kendra Nelson, Gonghua Pan, Leslie Pustilnik, Kristina Rafidi, Ann Marie Rossi, Rick Shepard, Stefanus Steyn, Chunyan Su, Shusen Sun, Kostantinos Tsaparikos, Courtney Williams, Jun Xiao, Kwansik Yoon, Xumiao Zhao
Journal: Cancer Research (2008)

LB-147  Over expression and amplification of Aurora-2, a key regulator of mitosis plays important but distinct roles in the G2 and M phases of the cell cycle and has been reported in different tumor types including breast, colon, pancreatic, ovarian and gastric cancer. We report herein the discovery and preclinical profile of PF-3814735, a novel heretofore unreported pyrimidine scaffold based ATP-competitive, reversible inhibitor of Aurora-1 and 2 kinases. SAR at the C2 and C4 positions of the pyrimidine scaffold led to a series with great in vitro potency. Subsets of analogs from this series that demonstratedexcellent in vitro ADME profile were selected for further in vivo pharmacological and ADME profiling. These efforts led to the discovery of PF-3814735, which inhibits Aurora-1 kinase with an IC50 value of 0.8 nM and Aurora-2 kinase with an IC50 value of 5 nM and has corresponding potent cellular and biochemical activity. Oral administration of PF-3814735 demonstrated in vivo pharmacology and high oral bioavailability (%F>50). Treatment with PF-3814735 resulted in significant tumor growth inhibition at tolerable doses in multiple tumor xenograft models.  In summary, we will be describing the chemistry and SAR that led to the discovery of a potent Aurora kinase inhibitor, PF-3814735 that is the clinical candidate and is currently in Phase I trials. Design,synthesis, inhibitor kinase and cell activity, kinase selectivityprofile, ADME as well as inhibitor chemical structure will be presented.
Mast cells generated from patients with atopic eczema have enhanced levels of granule mediators and an impaired Dectin-1 expression
Authors: C. Ribbing, C. Engblom, J. Lappalainen, K. Lindstedt, P. T. Kovanen, M. A. Karlsson, L. Lundeberg, C. Johansson, G. Nilsson, C. Lunderius-Andersson, A. Scheynius
Journal: Allergy (2010)

To cite this article: Ribbing C, Engblom C, Lappalainen J, Lindstedt K, Kovanen PT, Karlsson MA, Lundeberg L, Johansson C, Nilsson G, Lunderius-Andersson C, Scheynius A. Mast cells generated from patients with atopic eczema have enhanced levels of granule mediators and an impaired Dectin-1 expression. Allergy 2011; 66: 110–119. Background: The disrupted skin barrier of patients with atopic eczema (AE) might facilitate contact between mast cells (MCs) in the skin and environmental triggers of the disease. One such trigger is the skin-colonizing yeast Malassezia sympodialis (M. sympodialis). In this study, we investigated the interaction of MC with M. sympodialis. Methods: Mast cells were generated from peripheral blood CD34+ progenitor cells of healthy controls (HC) and M. sympodialis-sensitized AE patients. Biopsy specimens were taken from HC and lesional AE skin for immunohistological stainings. Results: The progenitor-derived MCs expressed the macrophage-inducible C-type lectin receptor Mincle, and exposure of these cells to M. sympodialis induced up-regulation of the mRNA expression of Mincle. Furthermore, we demonstrate that, when compared to HC, the progenitor-derived MCs from AE patients (i) contain more intrinsic granule mediators such as histamine, (ii) exhibit enhanced IL-6 release in response to M. sympodialis exposure, and (iii) have an impaired up-regulation of the fungal recognition receptor Dectin-1. In addition, analysis of skin sections from HC and AE patients revealed MCs as the predominant Dectin-1-expressing cell type in the skin. Conclusion: Our data indicate that progenitor-derived MCs from AE patients differ from those from HC. Further investigations with skin-derived MCs are necessary to confirm the observed differences which could provide new insights into the pathogenic mechanisms underlying AE.
Abstract 14710: Ideal Cardiovascular Health in Younger Age and Functional Disability in Older Age -- The Chicago Heart Association Detection Project in Industry (CHA) 32 Year Follow-up Health Survey
Authors: Thanh-Huyen T Vu, Kiang Liu, Donald M Lloyd-Jones, Daniel B Garside, Martha L Daviglus
Journal: Circulation (2014)

Background: Ideal levels of all major cardiovascular disease (CVD) risk factors (RF), i.e., low risk (LR), in younger age are associated with lower subsequent CVD morbidity and mortality in older age. However, data are limited on the relationships of LR profile in younger age with functional disability in older age.

Methods: We used data from 3,669 men and 2,345 women from the CHA Study, ages 29-68 in 1967-73, free from major ECG abnormalities, history of diabetes, or MI at baseline with functional disability data from the 2003 health survey. Functional disability was categorized as having: 1)any disabilities in activities of daily living (ADL), 2)any disabilities in instrumental ADL(IADL) but no ADL, or 3) no disability. LR status [i.e., SBP/DBP (≤120/≤80 mmHg and no antihypertensive medication), serum total cholesterol (<200 mg/dl and no cholesterol-lowering medication), not smoking, BMI < 25 kg/m2, and no diabetes0] was assessed at baseline. Details on definitions of ADL/IADL disabilities and RF status are shown in Table footnote.

Results: Only 6% of participants were LR at baseline; follow-up mean age was 76.6 years, 11% of the cohort reported having IADL disabilities, and 7% having ADL disabilities. With multivariate-adjustment (see Table), baseline LR was associated with the lowest likelihood of having any ADL or IADL disabilities 32 years later (P-trends < 0.001). Compared to those with ≥2 RFs, the odds of having any ADL disabilities vs. no disability in persons with baseline LR, 0 RF, and 1RF were lower by 60%, 50%, and 40%, respectively. Similar results were observed for having any IADL disabilities.

Conclusion: Having an ideal CVD RF profile at younger age is associated with lowest functional disabilities in older age and thus can reduce the loss of independence and improve quality of life in older adults.

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Curbing the Diabetes Pandemic
Authors: Frank B. Hu, Ambika Satija, JoAnn E. Manson
Journal: JAMA (2015)

disease of the affluent, with lower socioeconomic groups being disproportionately affected in high-income countries and with 77% of the world’s diabetic population living in low- and middle-income countries. It is also no longer predominantly a disease of older persons, with almost half of the people with diabetes in the 40- to 59-year age range. Low- and middle-income countries face the added challenge of dealing with a dual burden of disease, as they are seeing an increase in obesity and diabetes levels, while still grappling with undernutrition and infectious diseases. 3 In 2013, diabetes was associated with US $548 billion in health care expenditures globally. 1 This figure is
Buruli Ulcer Successfully Treated With Negative-Pressure Wound Therapy
Authors: Chiaki Murase, Michihiro Kono, Kazue Nakanaga, Norihisa Ishii, Masashi Akiyama
Journal: JAMA Dermatology (2015)

no specific evidence of an autoimmune etiology.The patient was advised to discontinue using the brimonidine gel and to follow up in clinic in 1 week.At 1-week follow-up, her symptoms improved dramatically (Figure ,B), leading us to believe that her initial reaction was secondary to long-term brimonidine use.Discussion | Since its approval by the US Food and Drug Administration in 2013, topical brimonidine gel has offered effective therapy for certain patients with persistent facial erythema secondary to rosacea. 1 Previous studies reveal that most patients tolerate this therapy quite well without any adverse reactions. 2However, there have been reports of cutaneous adverse reactions at the site of brimonidine application.These include flushing, worsening erythema, burning sensation, and contact dermatitis, most of which present immediately or early in the course of therapy. 3Herein, we describe a patient who had been using brimonidine for nearly 7 months before developing what we believe to be a novel adverse drug reaction.Interestingly, our patient's symptoms were in areas surrounding the site of brimonidine use, sparing the tissue in direct contact with the gel.Brimonidine is a relatively selective α2 adrenergic agonist.Topical application causes vasoconstriction of superficial vessels at the site of application, allowing for the reduction of erythema.We hypothesize that the reaction seen in our patient represents a compensatory vasodilation of vessels in the surrounding skin due to chronic vasoconstriction at the site of long-term brimonidine use.Findings from history, physical examination, laboratory testing, and histopathologic examination ruled out several other etiologies, including photosensitivity and autoimmune conditions.We therefore conclude that this is a probable adverse drug reaction to brimonidine. 4A logical treatment for this adverse effect is discontinuation of brimoni-dine application.Because this is a relatively new therapy, these mechanisms are not well established, and further investigation is warranted.
CRYPTOCOCCUS MENINGITIS: REPORT OF CASE WITH SURVIVAL AFTER 14 MONTHS
Authors: H C ROBERTSON, V MOSELEY
Journal: Annals of Internal Medicine (1952)

Case Reports1 June 1952CRYPTOCOCCUS MENINGITIS: REPORT OF CASE WITH SURVIVAL AFTER 14 MONTHSHENRY C. ROBERTSON JR., M.D., VINCE MOSELEY, M.D., F.A.C.P.HENRY C. ROBERTSON JR., M.D.Search for more papers by this author, VINCE MOSELEY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-6-1538 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTorula invasion of the central nervous system is an uncommon occurrence, approximately 105 verified cases having been recorded since it was first reported by Busse in 1849. The disease is usually fatal, and there are no satisfactorily proved cases of recovery. The literature contains several excellent reviews of this subject, and it is not the purpose of this report to repeat these comprehensive discussions.The causative organism,Cryptococcus neoformans, perhaps more familiarly known asTorula histolytica, is a yeastlike organism which occurs normally in many types of grasses, insects, beeswax, pickle brine and milk. Strains have been isolated from the...Bibliography1. HamiltonThompson LCPE: Treatment of Cryptococcus meningitis with penicillin, Am. J. Dis. Child. 72: 334, 1946. CrossrefMedlineGoogle Scholar2. FlinnHookerScott LBJWEG: Torula histolytica infection, Delaware State M. J. 18: 141, 1946. MedlineGoogle Scholar3. MezeyFowler CMR: Cerebrospinal Cryptococcus, J. A. M. A. 132: 632, 1946. CrossrefMedlineGoogle Scholar4. LevinRoux WP: Torula infection of the central nervous system, South African M. J. 20: 2, 1946. MedlineGoogle Scholar5. GreeningMenville RRLJ: Roentgen findings in Torula, Radiology 48: 381, 1947. CrossrefMedlineGoogle Scholar6. Hassin GB: Torula of the central nervous system, J. Neuropath. and Exper. Neurol. 6: 44, 1947. CrossrefGoogle Scholar7. VoylesBeck GQEM: Systemic infection due to Torula histolytica , Arch. Int. Med. 77: 504, 1947. CrossrefGoogle Scholar8. GlobusGangBergman JHKMPS: Torula meningoencephalitis , J. Mt. Sinai Hosp. 16: 14, 1949. MedlineGoogle Scholar9. DeWanLefflerCollette CHRJTS: Case report of Cryptococcus meningitis, Guthrie Clin. Bull. 19: 75, 1949. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Charleston, South Carolina*Received for publication August 28, 1950.From the Department of Medicine, Medical College of the State of South Carolina, and Roper Hospital, Charleston, South Carolina. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCryptococcosisCryptococcosisDie tierischen Parasiten und Pilzinfektionen im zentralen Nervensystem 1 June 1952Volume 36, Issue 6Page: 1538-1540KeywordsAttentionCentral nervous systemCryptococcus neoformansErectile dysfunctionHospital medicineMeningitisMilk ePublished: 1 December 2008 Issue Published: 1 June 1952 PDF downloadLoading ...
A randomized, double‐blind, placebo‐controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis
Authors: A.B. Gottlieb, R.G. Langley, B.E. Strober, K.A. Papp, P. Klekotka, K. Creamer, E.H.Z. Thompson, M. Hooper, G. Kricorian
Journal: British Journal of Dermatology (2012)

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.
Anaesthesia is an unpopular specialty in the United States
Authors: C. Berry
Journal: BMJ (1996)

cancer units in district general hospitals.'It refers to the number of patients with common cancers whom surgeons need to treat to ensure adequate skill and suggests that figures regarded as adequate now will be revised upwards in the future.At present no firm recommendations exist about the critical number of patients who are required to ensure adequate clinical skill, though 50-80 per specialist has been suggested by the British Association of Surgical Oncology and the British Breast Group.The only evidence currently available suggests that outcome is bet- ter when the annual caseload per consultant exceeds 30 compared with under 10.2 Evidence from the same source showed a slightly worse (though not significant) outcome, with fewer patients receiving adjuvant treatments, when the caseload exceeded 50, but this has received no attention.The study concluded that improved survival could be explained by the introduction of a multidisciplinary approach to treatment and that the effect of patient numbers was probably a function of this and of clinical organisation.A recent paper suggested that the prognosis of patients with breast cancer is improved by specialist care.3A specialist interest was defined on the basis of four criteria: having a dedicated breast clinic, having a defined association with pathologists and oncologists, organising and facilitating clinical trials, and maintaining a separate record of all patients.The paper received some criticism (though general support results.
A perspective on re‐evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile
Authors: Kirkwood F. Adams, Jalal K. Ghali, J. Herbert Patterson, Wendy Gattis Stough, Javed Butler, Jerry L. Bauman, Hector O. Ventura, Hani Sabbah, John I. Mackowiak, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2014)
Microvascular injury in reperfused infarcted myocardium: noninvasive assessment with contrast-enhanced echoplanar magnetic resonance imaging 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
Authors: Jens Bremerich, Michael F Wendland, Håkan Arheden, Rolf Wyttenbach, Dong W Gao, John P Huberty, Michael W Dae, Charles B Higgins, Maythem Saeed
Journal: Journal of the American College of Cardiology (1998)
Abstract MP75: The Influence of Income on Global Dietary Habits by Country, Age, Sex, and Time
Authors: Dariush Mozaffarian, Shahab Khatibzadeh, Renata Micha, Andrew Muhammad
Journal: Circulation (2014)

Background: Income may influence diet, especially in low and middle-income countries, and particularly in the setting of relatively high recent food prices and the global financial crisis. Yet, the influence of income on dietary habits in most countries is not well established, nor how this influence varies by age, sex, or time across different countries. Aim: To assess the relation of income with dietary habits globally, including from least developed to highly industrialized countries, and by age, sex, and time. Methods: We estimated the income elasticities of consumption of 11 food categories in 180 countries using the Global Dietary Database, based on 325 national surveys on individual-level dietary intakes worldwide. Per-capita income by country in real terms and on purchasing power parity basis were obtained from the World Bank. Elasticities were modelled using a modified Working’s expenditure share model by country, age (20-80+ in 5-year intervals), sex, and time (1990, 2005, 2010). Results: Significant income elasticities were identified. Food intake in low-income countries was generally more responsive to income than in high-income countries ( Figure ). In addition, income elasticity of dietary intake varied for different items (fruit, fruit juices, vegetables, beans/legumes, nuts/seeds, whole grains, unprocessed red meat, processed meat, milk, sugar sweetened beverages, fish). Additional heterogeneity was evident by age and sex, that also varied by food item. Conclusions: Intakes of different foods are variably responsive to income, and diets in low-income countries are more sensitive to income changes than in high-income countries, even after accounting for purchasing power. Additional food-specific patterns of variation in income elasticity were seen by age and sex. These first-ever global findings of dietary income elasticity based on individual-reported dietary intakes and by age and sex inform the relevance and impact of underlying societal determinants of dietary habits across the world.