tbuckley/cabot-search huggingface dataset:
Analysis of the inotropic:chronotropic selectivity of dobutamine and dopamine in anaesthetised dogs and guinea-pig isolated atria
Authors: P. LUMLEY, K. J. BROADLEY, G. P. LEVY
Journal: Cardiovascular Research (1977)

The previously reported in vivo inotropic selectivity of dobutamine and dopamine compared with isoprenaline has been demonstrated in anaesthetised bivagotamised open chest dogs. Responses of heart rate, right ventricular tension, left ventricular dP/dtmax, and blood pressure were measured. Compared with isoprenaline, dobutamine and dopamine were 1.8 and 2.4 times more active in increasing cardiac contractility than rate. The inotropic selectivity of dopamine but not that of dobutamine was abolished by pretreatment of dogs with syrosingopine. In guinea-pig isolated atria, isoprenaline, dobutamine, and dopamine were all slightly rate selective although this was less for dopamine. In atria incubated with phenoxybenzamine from guinea-pigs pretreated with reserpine only the dopamine dose-response curves were displaced to the right indicating a considerable indirect sympathomimetic component. The in vivo inotropic selectivity of dopamine could therefore be explained on the basis of this indirect activity being manifested at lower doses in the myocardium where the stores of catecholamines are more abundant than at the sinoatrial node. However, it is concluded that the inotropic selectivity of dobutamine seen in vivo is not due to indirect activity, reflex effects, or to a difference in the beta-adrenoceptors mediating the rate and tension responses of the heart. Possible alternative explanations are discussed.
Option appraisal of population-based colorectal cancer screening programmes in England
Authors: P. Tappenden, J. Chilcott, S. Eggington, H. Sakai, J. Karnon, J. Patnick
Journal: Gut (2006)

<b>Objectives:</b> To estimate the effectiveness, cost-effectiveness and resource impact of faecal occult blood testing (FOBT) and flexible sigmoidoscopy (FSIG) screening options for colorectal cancer to inform the Department of Health's policy on bowel cancer screening in England. <b>Methods:</b> We developed a state transition model to simulate the life experience of a cohort of individuals without polyps or cancer through to the development of adenomatous polyps and malignant carcinoma and subsequent death in the general population of England. The costs, effects and resource impact of five screening options were evaluated: (a) FOBT for individuals aged 50–69 (biennial screening); (b) FOBT for individuals aged 60–69 (biennial screening); (c) once-only FSIG for individuals aged 55; (d) once-only FSIG for individuals aged 60; and (e) once-only FSIG for individuals aged 60, followed by FOBT for individuals aged 61–70 (biennial screening). <b>Results:</b> The model suggests that screening using FSIG with or without FOBT may be cost-saving and may produce additional benefits compared with a policy of no screening. The marginal cost-effectiveness of FOBT options compared to a policy of no screening is estimated to be below £3000 per quality adjusted life year gained. <b>Conclusions:</b> Screening using FOBT and/or FSIG is potentially a cost-effective strategy for the early detection of colorectal cancer. However, the practical feasibility of alternative screening programmes is inevitably limited by current pressures on endoscopy services.
Anatomy of the sural nerve in a computer-assisted model: implications for surgical minimal-invasive Achilles tendon repair
Authors: Musa Citak, Karsten Knobloch, Knut Albrecht, Christian Krettek, Tobias Hufner
Journal: British Journal of Sports Medicine (2007)

Sural nerve injuries are an evident risk especially of minimal-invasive surgical Achilles tendon repair. However, detailed anatomical studies focusing on the relationship of the sural nerve with the Achilles tendon at various levels are scarce, even pending in two planes.To determine the position and course of the sural nerve in relation to the Achilles tendon in two planes after trans-section and computer-assisted determination.The exact course of the sural nerve was determined in 10 cadavers (55.3 years, 19-89 years), using a computer-assisted method in two planes (transversal/sagittal).The sural nerve crossed the Achilles tendon at 11 (8.7-12.4) cm proximal to the tuber calcanei. The distance between the lateral crossing and the proximal musculotendineus junction was 35 (20-58) mm. Starting from the tuber calcanei, the distance was 2/2 mm (transversal/sagittal plane) at 11 cm proximal to the tuber calcanei, 4/4 mm at 10 cm proximal, 5/6 mm at 9 cm, 8/10 mm at 5 cm and 11/18 mm at the tuber calcanei.In the lateral crossing region of the sural nerve and the lateral proximal Achilles tendon 9-12 cm proximal to the tuber calcanei, a close relationship of both anatomical structures can be visualised using computer-assisted measurements; caution is suggested to prevent sural nerve entrapment in either open or percutaneous Achilles tendon repair.
The deviating eyes of Michelangelo's David
Authors: S. Shaikh
Journal: Journal of the Royal Society of Medicine (2005)

In 1501 Michelangelo received a commission from the Guild of Wool Merchants of Florence to carve out a giant statue for one of the buttresses of the Cathedral of Florence. The David was started in 1501 when Michelangelo was only 26 years of age, and finished in 1504, when he was not yet 30, and stands as a testament to Michelangelo’s mastery of the human form and sculpture. Previous works had shown the subject just after he had slain and beheaded Goliath. Michelangelo’s David broke new ground by depicting a ‘most beautiful animal preparing to kill—not by savagery and brute force, but by intellect and skill’.1 Direct anatomical dissection was forbidden during the Renaissance and artists who wished to view the inside of the human body had to do so almost in secret. When Michelangelo fashioned a life-sized wooden crucifix altarpiece for the Santo Spirito in Florence, the prior allowed him access to bodies awaiting burial.2 The practice of anatomy became a passion for Michelangelo and his works correctly demonstrated numerous anatomical structures. He even contemplated publishing a treatise on anatomy together with his physician, Realdo Colombo, who treated him for kidney stones and later rose to become professor and medical consultant to the Vatican.3 So real were Michelangelo’s works that they were used as models by other artists of the era and for centuries afterwards. In addition, ‘pathological’ features in his paintings and sculptures have attracted much attention in medical journals.4 For all Michelangelo’s mastery of human anatomy, the David possesses certain anatomical imperfections. The right hand is bigger than the left with an enlarged abductor digiti minimi—suggested as a device to draw attention to the stone as a symbol of his courage and physical power.5 Yet the most significant anomaly is in the David ’s eyes, which seem to manifest an exodeviation. The right eye is in the primary position while the left eye appears to be looking out to the left (Figure 1). The likely reason why this detail has been unrecognized for hundreds of years is that most viewers have been physically unable to examine the David at eye level and at arms-length. The statue, about 5 metres tall in addition to its supporting pedestal, was meant to be viewed from below and, presumably, at a distance. In 1999, the Digital Michelangelo Project, led by Stanford University and Marc Levoy, professor of computer science and engineering, rendered a three-dimensional computer model that permitted the work to be viewed from different angles and with varying light intensity and colour modulation.6 A digitally rendered direct frontal image—a perspective not easily attainable by photography and
The role of vocalization, memory retrieval, and external symbols in cognitive evolution
Authors: Merlin Donald
Journal: Behavioral and Brain Sciences (1996)

Abstract The human vocal apparatus is part of a vertically integrated system, and I agree with Licbennan that modern high-speed phonology co-evolved with our capacity for grammar. Olson and I agree that some distinctly human thought skills appear to be fairly recent cultural acquisitions related to the introduction of new symbolic technologies and external (that is, nonbiological) memory storage. Stenning 's concern with my use of the term “episodic” can be resolved by distinguishing between episodic storage and retrieval. Baum 's suggestions regarding courtship and cognitive evolution seem to apply better to mimetic expression than to language.
Biomechanics and tennis
Authors: B Elliott
Journal: British Journal of Sports Medicine (2006)

Success in tennis requires a mix of player talent, good coaching, appropriate equipment, and an understanding of those aspects of sport science pertinent to the game. This paper outlines the role that biomechanics plays in player development from sport science and sport medicine perspectives. Biomechanics is a key area in player development because all strokes have a fundamental mechanical structure and sports injuries primarily have a mechanical cause.
Variability of Phase Shift Between Blood Pressure and Heart Rate Fluctuations
Authors: Josef Halámek, Tomáš Kára, Pavel Jurák, Miroslav Souček, Darrel P. Francis, L. Ceri Davies, Win K. Shen, Andrew J.S. Coats, Miroslav Novák, Zuzana Nováková, Roman Panovský, Jiří Toman, Josef Šumbera, Virend K. Somers
Journal: Circulation (2003)

We postulated that the variability of the phase shift between blood pressure and heart rate fluctuation near the frequency of 0.10 Hz might be useful in assessing autonomic circulatory control.We tested this hypothesis in 4 groups of subjects: 28 young, healthy individuals; 13 elderly healthy individuals; 25 patients with coronary heart disease; and 19 patients with a planned or implanted cardioverter-defibrillator (ICD recipients). Data from 5 minutes of free breathing and at 2 different, controlled breathing frequencies (0.10 and 0.33 Hz) were used. Clear differences (P<0.001) in variability of phase were evident between the ICD recipients and all other groups. Furthermore, at a breathing frequency of 0.10 Hz, differences in baroreflex sensitivity (P<0.01) also became evident, even though these differences were not apparent at the 0.33-Hz breathing frequency.The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure-RR interactions become evident. These interactions, whether computed as a variability of phase to define stability of the blood pressure-heart rate interaction or defined as the baroreflex sensitivity to define the gain in heart rate response to blood pressure changes, are significantly different in patients at risk for sudden arrhythmic death. In young versus older healthy individuals, only baroreflex gain is different, with the variability of phase being similar in both groups. These measurements of short-term circulatory control might help in risk stratification for sudden cardiac death.
Conservation of unique cell-surface CD antigen mosaics in HIV-1–infected individuals
Authors: Adrian Woolfson, Justin Stebbing, Brian D. M. Tom, Kerryn J. Stoner, Walter R. Gilks, David P. Kreil, Stephen P. Mulligan, Larissa Belov, Jeremy S. Chrisp, Will Errington, Adrian Wildfire, Wendy N. Erber, Mark Bower, Brian Gazzard, Richard I. Christopherson, Mike A. Scott
Journal: Blood (2005)
Open access and openly accessible: a study of scientific publications shared via the internet
Authors: Jonathan D Wren
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To determine how often reprints of scientific publications are shared online, whether journal readership level is a predictor, how the amount of file sharing changes with the age of the article, and to what degree open access publications are shared on non-journal websites. <b>Design</b> The internet was searched using an application programming interface to Google, a popular and freely available search engine. <b>Main outcome measures</b> The proportion of reprints of journal articles published between 1994 and 2004 from within 13 subscription based and four open access journals that could be located online at non-journal websites. <b>Results</b> The probability that an article could be found online at a non-journal website correlated with the journal impact factor and the time since initial publication. Papers from higher impact journals and more recent articles were more likely to be located. On average, for the high impact journal articles published in 2003, over a third could be located at non-journal websites. Similar trends were observed for the delayed or full open access publications. <b>Conclusions</b> Decentralised sharing of scientific reprints through the internet creates a degree of de facto open access that, though highly incomplete in its coverage, is none the less biased towards publications of higher popular demand.
iNOS Gene Expression Modulates Microvascular Responsiveness in Endotoxin-Challenged Mice
Authors: Walter A. Boyle, Lakshmi S. Parvathaneni, Virginie Bourlier, Craig Sauter, Victor E. Laubach, J. Perren Cobb
Journal: Circulation Research (2000)

Abstract —Septic shock is characterized by vasodilation and decreased responsiveness to vasoconstrictors. Recent studies suggest this results from nitric oxide (NO) overproduction after expression of the calcium-independent isoform of NO synthase (iNOS) in smooth muscle cells. However, direct evidence linking iNOS (NOS2) expression and decreased microvascular responsiveness after septic stimuli is lacking. In the present study, we determined the effect of bacterial lipopolysaccharide (LPS, 20 mg/kg, IP) on smooth muscle contraction and endothelial relaxation in mesenteric resistance arteries from wild-type and iNOS knockout mice. Four hours after challenge with LPS or saline in vivo, concentration-dependent responses to norepinephrine (NE) and acetylcholine (NE+ACh) were measured in cannulated, pressurized vessels ex vivo. In vessels from wild-type mice, NE-induced contraction was markedly impaired after LPS, and pretreatment with the iNOS inhibitor aminoguanidine (AG) partly restored the NE contraction. In contrast, NE contraction in microvessels from iNOS knockout mice was unaffected by LPS. ACh-induced relaxation was unaffected by LPS in vessels from either genotype. These data provide direct evidence that iNOS gene expression mediates the LPS-induced decrease in microvascular responsiveness to vasoconstrictors. Moreover, the observation that AG did not fully restore NE contraction after LPS, whereas iNOS gene deficiency did, suggests that iNOS expression plays a central role in the development of the NO-independent effect of LPS on microvascular responsiveness. Finally, our data indicate that LPS or iNOS expression has little effect on endothelium-dependent relaxation, and eNOS activity does not appear to play a role in the decreased smooth muscle responsiveness after LPS in this model. The full text of this article is available at http://www.circresaha.org.
Differential Regulation of p90 Ribosomal S6 Kinase and Big Mitogen–Activated Protein Kinase 1 by Ischemia/Reperfusion and Oxidative Stress in Perfused Guinea Pig Hearts
Authors: Yasuchika Takeishi, Jun-ichi Abe, Jiing-Dwan Lee, Hisaaki Kawakatsu, Richard A. Walsh, Bradford C. Berk
Journal: Circulation Research (1999)

Abstract —Reactive oxygen species (ROS) activate members of the Src kinase and mitogen-activated protein kinase superfamily, including big mitogen-activated protein kinase 1 (BMK1) and extracellular signal-regulated kinases (ERK1/2). A potentially important downstream effector of ERK1/2 is p90 ribosomal S6 kinase (p90RSK), which plays an important role in cell growth through the activation of several transcription factors, as well as the Na + /H + exchanger. Previously, we showed that Src regulates BMK1 via a redox-sensitive signaling pathway. Because ROS are generated during ischemia and reperfusion after ischemia, we assessed the effects of these stimuli (H 2 O 2 , ischemia, and reperfusion) in the activation of ERK1/2, p90RSK, Src, and BMK1 in perfused guinea pig hearts. H 2 O 2 (100 μmol/L) significantly activated all kinases. Ischemia alone stimulated p90RSK, Src, and BMK1 but not ERK1/2. These results suggest that p90RSK activation through ischemia occurs via a pathway other than ERK1/2. A role of Src in ischemia-mediated BMK1 activation was demonstrated through inhibition with the Src inhibitor 4-amino-5-(4-chlorophenyl)-7-( t -butyl)pyrazolo[3,4- d ]pyrimidine. Reperfusion after ischemia stimulated both p90RSK and ERK1/2. In contrast, although ROS increase during reperfusion after ischemia, the activities of both BMK1 and its upstream regulator, Src, were markedly attenuated by reperfusion after ischemia. The activation of C-terminal Src kinase during ischemia but not during reperfusion suggests that the attenuation of Src and BMK1 activity by reperfusion was not regulated by C-terminal Src kinase activity. The antioxidant N -2-mercaptopropionylglycine completely inhibited ERK1/2 and p90RSK activation by reperfusion but only partially inhibited ischemia-induced Src and BMK1 activation. The present study is the first to show the coregulation of Src and BMK1 by reperfusion after ischemia, which we propose to occur via a novel, ROS-independent pathway.
Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors
Authors: Bart C. Kuenen, Lee Rosen, Egbert F. Smit, Mandy R.N. Parson, Marcel Levi, Rita Ruijter, Holger Huisman, Marc A. Kedde, Paul Noordhuis, Wim J.F. van der Vijgh, Godefridus J. Peters, Gillian F. Cropp, Paul Scigalla, Klaus Hoekman, Herbert M. Pinedo, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To investigate the feasibility and pharmacokinetics of the combination cisplatin, gemcitabine, and SU5416. PATIENTS AND METHODS: Patients received cisplatin 80 mg/m2 on day 1, gemcitabine 1,250 mg/m2 on days 1 and 8, repeated every 3 weeks, and SU5416 (85 and 145 mg/m2) intravenously twice weekly. Pharmacokinetics of all three agents, side effects, and antitumor response were investigated in patients with solid tumors amenable to therapy with cisplatin/gemcitabine. RESULTS: In the first cohort of three patients entered at the 85 mg/m2 dose, no dose-limiting toxicities were observed. In the next cohort (145 mg/m2), three patients developed a thromboembolic event. After entry was restricted to patients with low thromboembolic risk, three additional patients enrolled at 145 mg/m2 developed a thromboembolic event. The dose was then reduced to 85 mg/m2 in all patients still on the study, and three additional patients were entered on this dose level. In 19 treated patients, eight patients developed nine thromboembolic events (three transient ischemic attacks, two cerebrovascular accidents, and four deep venous thromboses). The most common toxicities observed were those previously reported for SU5416 alone (headache and phlebitis) and for this chemotherapy regimen (nausea, thrombocytopenia, and leucopenia). No significant pharmacologic interaction among the three drugs was observed. Response rates were similar to those expected in the patient population selected for this study. Analysis of variables of the coagulation cascade and of vessel wall activation was performed in three patients and showed significant increases in thrombin generation and endothelial cell perturbation in a treatment cycle–dependent manner. CONCLUSION: The incidence of thromboembolic events, possibly related to the particular regimen tested in this study, discourages further investigation of this regimen.
Gene Deletion Screen for Cardiomyopathy in Adult <i>Drosophila</i> Identifies a New Notch Ligand
Authors: Il-Man Kim, Matthew J. Wolf, Howard A. Rockman
Journal: Circulation Research (2010)

Rationale : Drosophila has been recognized as a model to study human cardiac diseases. Objective : Despite these findings, and the wealth of tools that are available to the fly community, forward genetic screens for adult heart phenotypes have been rarely performed because of the difficulty in accurately measuring cardiac function in adult Drosophila . Methods and Results : Using optical coherence tomography to obtain real-time analysis of cardiac function in awake Drosophila , we performed a genomic deficiency screen in adult flies. Based on multiple complementary approaches, we identified CG31665 as a novel gene causing dilated cardiomyopathy. CG31665 , which we name weary ( wry ), has structural similarities to members of the Notch family. Using cell aggregation assays and γ-secretase inhibitors we show that Wry is a novel Notch ligand that can mediate cellular adhesion with Notch expressing cells and transactivates Notch to promote signaling and nuclear transcription. Importantly, Wry lacks a DSL (Delta-Serrate-Lag) domain that is common feature to the other Drosophila Notch ligands. We further show that Notch signaling is critically important for the maintenance of normal heart function of the adult fly. Conclusions : In conclusion, we identify a previously unknown Notch ligand in Drosophila that when deleted causes cardiomyopathy. Our study suggests that Notch signaling components may be a therapeutic target for dilated cardiomyopathy.
Peroxisome Proliferator–Activated Receptor Ligand Bezafibrate for Prevention of Type 2 Diabetes Mellitus in Patients With Coronary Artery Disease
Authors: Alexander Tenenbaum, Michael Motro, Enrique Z. Fisman, Ehud Schwammenthal, Yehuda Adler, Ilan Goldenberg, Jonathan Leor, Valentina Boyko, Lori Mandelzweig, Solomon Behar
Journal: Circulation (2004)

Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period.The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16).Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.