tbuckley/cabot-search huggingface dataset:
<i>Circulation Research</i> Launches Into Social Media
Authors: Roberto Bolli, Jonathan Schultz, Kara Hansell Keehan
Journal: Circulation Research (2010)

A s part of our plans, announced in a recent Editorial, 1 to dramatically expand the online presence of Circulation Research, we are pleased to announce the journal's foray into the social media sites Facebook and Twitter.The novel and groundbreaking work published in Circulation Research must be easily available and shareable in order to reach its full impact.Facebook and Twitter provide unique online opportunities to disseminate the latest advances in cardiovascular research published in Circulation Research to a wider audience of followers and fans beyond the confines of the traditional print journal product.As with other new developments at
Microvascular Hypersensitivity Subsequent to Chemical Denervation
Authors: SILVIO BAEZ, AARON F. KOPMAN, LOUIS R. ORKIN
Journal: Circulation Research (1967)

Microscopic observation and micrometric measurements of microarterial vessels in the mesentery of the anesthetized rat, during chemical interference with the vasomotor nerve supply, showed (A) marked (average 25x) hypersensitization to epinephrine; (B) persistent vasoconstriction; and (C) depression or cessation of vasomotion. These and concomitant similar reactions of the precapillary sphincter resulted in relative ischemia and frequent reversal of blood flow through the endothelial capillary network. A comparable hypersensitization to epinephrine, observed in six isolated perfused microarterial vessels, upon shift in internal static pressure strongly suggests that the change in reactivity of the vascular smooth muscle cell seen in vivo might also be related to a local change in transmural pressure. The plot of the logarithm of epinephrine threshold concentration vs. the approximate circumferential wall tension (computed for selected in vivo and in vitro experiments neglecting wall thickness) showed a steep rise in vessel sensitivity occurring concomitantly with decrease in wall tension. Thus it appears that hypersensitization of microarterial muscle cells which develops during the hypotensive episode of acute chemical nerve blockade in the rat may be primarily related to a modification in wall tension.
Blood pressure regulation in end-stage renal disease and anephric man.
Authors: G Onesti, K E Kim, J A Greco, E T del Guercio, M Fernandes, C Swartz
Journal: Circulation Research (1975)

The hemodynamic pattern of response to bilateral nephrectomy was studied in 29 patients with end-stage renal disease on maintenance hemodialysis. Four patterns of hemodynamic response were seen. In 12 patients with nonmalignant hypertension, bilateral nephrectomy reduced blood pressure and total peripheral resistance with no effects on cardiac output. In 5 patients with malignant hypertension, bilateral nephrectomy reduced blood pressure, increased cardiac index, and reduced total peripheral resistance more markedly. In these two groups, at equivalent levels of total exchangeable sodium, before and after bilateral nephrectomy, mean arterial pressure and total peripheral resistance were invaribly lower in the absence of renal tissue. In 3 additional patients with nonmalignant hypertension, the decrease in blood pressure after bilateral nephrectomy was delayed from 3 to 12 weeks. When this occurred spontaneously, it was accompanied by a decrease in total peripheral resistance. The fourth hemodynamic pattern was seen in 6 normotensive patients with end-stage renal disease. After bilateral nephrectomy, there were no significant changes in mean arterial pressure, total peripheral resistance, or cardiac output. Salt and water loading failed to elevate blood pressure significantly. Renal transplantation was performed in 3 hypertensive patients before removal of the end-stage kidney. The functioning renal homograft did not result in normal blood pressure as long as the end-stage kidneys remained in place. Removal of the end-stage kidneys significantly decreased mean arterial pressure and total peripheral resistance. In the anephric state, a sharp difference was seen in blood pressure response to salt and water loading between previously normotensive and previously hypertensive patients. Previously hypertensive patients responded with a progressive increase in blood pressure that reached hypertensive levels. Previously normotensive patients failed to elevate their blood pressure significantly. It is concluded that the vasopressor function of the kidney is the most important factor in the pathophysiology of hypertension of end-state renal disease. Expansion of body fluid plays a role, but elevates the blood pressure only in patients who were previously hypertensive. The antihypertensive function of the kidney does not appear to be a major factor in the regulation of blood pressure in end-stage renal disease.
A model for predicting life expectancy of children with cystic fibrosis
Authors: P. Aurora, A. Wade, P Whitmore, B Whitehead
Journal: European Respiratory Journal (2000)

In this study the authors aimed to produce a model for predicting the life expectancy of children with severe cystic fibrosis (CF) lung disease. The survival of 181 children with severe CF lung disease referred for transplantation assessment 1988-1998 (mean age 11.5 yrs, median survival without transplant 1.9 yrs from date of assessment) were studied. Proportional hazards modelling was used to identify assessment measurements that are of value in predicting longevity. The resultant model included low height predicted forced expiratory volume in one second (FEV1), low minimum oxygen saturation (Sa,O2min) during a 12-min walk, high age adjusted resting heart rate, young age, female sex, low plasma albumin, and low blood haemoglobin as predictors for poor prognosis. Extrapolation from the model suggests that a 12-yr old male child with an FEV1 of 30% pred and a Sa,O2min of 85% has a 44% risk of death within 2 yrs (95% confidence interval (CI) 35-54%), whilst a female child with the same measurements has a 63% risk of death (95% CI 52-73%) within the same period. The model produced may be of value in predicting the life expectancy of children with severe cystic fibrosis lung disease and in optimizing the timing of lung transplantation.
Erythrocyte membrane rigidity induced by glycophorin A-ligand interaction. Evidence for a ligand-induced association between glycophorin A and skeletal proteins.
Authors: J A Chasis, N Mohandas, S B Shohet
Journal: Journal of Clinical Investigation (1985)

Erythrocyte skeletal proteins are known to play an important role in determining membrane deformability. In order to see whether transmembrane proteins also influence deformability and, if so, whether this influence is mediated by an interaction with the membrane skeleton, we examined the effect on deformability of ligands specific for transmembrane proteins. We found membrane deformability markedly reduced in erythrocytes that were pretreated with glycophorin A-specific ligands. In contrast, ligands specific for band 3 and A and B blood group antigens had no effect. The increase in membrane rigidity appeared to depend upon a transmembrane event and not upon a rigidity-inducing lattice on the outside surface of the cell in that a monovalent Fab of antiglycophorin IgG caused decreased deformability. We therefore looked for a ligand-induced association of glycophorin and the skeletal proteins and found, in Triton X-100-insoluble residues, a partitioning of glycophorin with the skeletal proteins only after preincubation with a ligand specific for glycophorin. We then studied cells and resealed membranes with skeletal protein abnormalities. In spectrin-deficient and protein 4.1-deficient erythrocytes and in 2,3-diphosphoglycerate-treated resealed membranes, the antiglycophorin IgG was only one-third as effective in decreasing deformability as it was in normal cells. Thus, normal skeletal proteins appear to be essential for liganded glycophorin to affect membrane deformability maximally. Taken together, these observations indicate that there is a ligand-induced interaction between glycophorin A and skeletal proteins and that this interaction can directly influence membrane deformability.
Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study
Authors: R. Hadfield
Journal: Human Reproduction Update (1997)

The autopsy records between 1980 and 1995 of 399 female rhesus monkeys (Macaca mulatta) at the Wisconsin Regional Primate Research Center were examined. Spontaneous endometriosis was found in 81 (20%) of the animals. The mean (±SD) ages at death for animals with and without endometriosis were 20.7±5.5 (range 10-35) and 13.4±7.7 (range 4-37) years respectively. Many of the animals had been exposed to experimental procedures, including laparoscopies, hysterotomies and oestradiol implants, and these were examined as possible risk factors for endometriosis. Of the 81 affected animals, 62 were matched to unaffected controls for age at death (to within 1 year) and year of death (to within 2 years) and the effect of various factors on the development of endometriosis was determined using conditional logistic regression. Exposure to three or more oestradiol implants or one or more hysterotomies were both significant risk factors, with estimated relative risks of 9.7 (95% confidence interval 2.5-37.2) and 5.8 (95% confidence interval 1.6-20.2) respectively. Animals that had been exposed to one or more laparoscopies showed no increased risk for developing endometriosis. These findings provide insight into the aetiology of the disease in women.
Modulation of Pulmonary Leukotriene B4 Production by Cyclooxygenase-2 Inhibitors and Lipopolysaccharide
Authors: Jenny T. Mao, I-Hsien Tsu, Steven M. Dubinett, Bradley Adams, Theodore Sarafian, Felicita Baratelli, Michael D. Roth, Kenneth J. Serio
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Emerging data continue to link carcinogenesis to inflammatory events involving the eicosanoid metabolic pathways. We therefore evaluated the effects of cyclooxygenase (COX)-2 inhibition on leukotriene (LT) B4 synthesis in the lungs of active smokers, as part of a pilot lung cancer chemoprevention study with celecoxib (Celebrex), an oral COX-2 inhibitor. Experimental Design: Bronchoalveolar lavage was performed before celecoxib treatment and after 1 month of celecoxib treatment to recover alveolar macrophages (AMs) and lining fluid for study. After harvest, AMs were immediately stimulated in vitro with the calcium ionophore A23187. AMs obtained from smokers before treatment and from ex-smoker control subjects were also cultured overnight with SC58236, a selective COX-2 inhibitor, with or without lipopolysaccharide stimulation. Results: Treatment with oral celecoxib only modestly increased LTB4 levels in bronchoalveolar lavage, without increasing the mRNA transcription of 5-lipoxygenase (5-LOX) or 5-LOX-activating protein in AMs, whereas the acute calcium ionophore-stimulated LTB4 production from smokers’ AMs was markedly increased by 10.6-fold. In addition, smokers’ AMs were twice as responsive in producing LTB4 when exposed to lipopolysaccharide compared with ex-smokers’ AMs. Concomitant COX-2 inhibition with SC58236, however, did not significantly impact these changes, whereas the 5-LOX inhibitor Zileuton blocked the generation of LTB4 in a dose-responsive manner. Finally, cycloheximide increased the production of LTB4 under all conditions, suggesting a shunting phenomenon and/or the presence of pathway inhibitors. Conclusions: Our findings suggest that whereas oral celecoxib is capable of modulating LTB4 production in the lung microenvironment, under physiologic conditions, this effect is probably not functionally significant.
Common Variation in the NOS1AP Gene Is Associated With Drug-Induced QT Prolongation and Ventricular Arrhythmia
Authors: Yalda Jamshidi, Ilja M. Nolte, Chrysoula Dalageorgou, Dongling Zheng, Toby Johnson, Rachel Bastiaenen, Suzanne Ruddy, Daniel Talbott, Kris J. Norris, Harold Snieder, Alfred L. George, Vanessa Marshall, Saad Shakir, Prince J. Kannankeril, Patricia B. Munroe, A. John Camm, Steve Jeffery, Dan M. Roden, Elijah R. Behr
Journal: Journal of the American College of Cardiology (2012)
30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study
Authors: Gianni Bonadonna, Angela Moliterni, Milvia Zambetti, Maria Grazia Daidone, Silvana Pilotti, Luca Gianni, Pinuccia Valagussa
Journal: BMJ (2005)

The review centers on chemical, chromatographic, and electrometric methods of oxygen analysis used in the study of parenteral solutions. Basic principles in each of the methods of analysis are presented along with indications of their sensitivities, advantages, and drawbacks. The past and current literature shows the Winkler method to be the bench mark for the development or modification of virtually any technique for dissolved oxygen measurements. Electrometric methods, most notably that using the membrane covered polarographic detector, appear to be the most promising in terms of generating rapid, accurate results.
<i>PIK3CA, BRAF</i>, and PTEN Status and Benefit from Cetuximab in the Treatment of Advanced Colorectal Cancer—Results from NCIC CTG/AGITG CO.17
Authors: Christos S. Karapetis, Derek Jonker, Manijeh Daneshmand, Jennifer E. Hanson, Christopher J. O'Callaghan, Celia Marginean, John R. Zalcberg, John Simes, Malcolm J. Moore, Niall C. Tebbutt, Timothy J. Price, Jeremy D. Shapiro, Nick Pavlakis, Peter Gibbs, Guy A. Van Hazel, Ursula Lee, Rashida Haq, Shakeel Virk, Dongsheng Tu, Ian A.J. Lorimer
Journal: Clinical Cancer Research (2013)

Cetuximab improves survival in patients with K-ras wild-type advanced colorectal cancer. We examined the predictive and prognostic significance of additional biomarkers in this setting, in particular BRAF, PIK3CA, and PTEN.Available colorectal tumor samples were analyzed from the CO.17 study. BRAF mutations were identified in tumor-derived DNA by direct sequencing and PIK3CA mutations were identified using a high-resolution melting screen with confirmation by sequencing. PTEN expression by immunohistochemistry (IHC) was performed on tissue microarrays. For each biomarker, prognostic and predictive effects were examined using a Cox model with tests for treatment-biomarker interaction.A total of 572 patients with pretreated colorectal cancer were randomly assigned to receive cetuximab or best supportive care (BSC). Of 401 patients assessed for BRAF status, 13 (3.2%) had mutations. Of 407 patients assessed for PIK3CA status, 61 (15%) had mutations. Of 205 patients assessed for PTEN, 148 (72%) were negative for IHC expression. None of BRAF, PIK3CA, or PTEN was prognostic for overall or progression-free survival in the BSC arm. None was predictive of benefit from cetuximab, either in the whole study population or the K-ras wild-type subset. In the K-ras wild-type subgroup, the overall survival adjusted HR according to BRAF mutation status was 1.39 (interaction P = 0.69), PIK3CA mutation status HR = 0.79 (interaction P = 0.63), and PTEN expression HR = 0.75 (interaction P = 0.61).In chemotherapy-refractory colorectal cancer, neither PIK3CA mutation status nor PTEN expression were prognostic, nor were they predictive of benefit from cetuximab. Evaluation of predictive significance of BRAF mutations requires a larger sample size.
Effect of Chronic Hyperinflation on Diaphragm Length and Surface Area
Authors: MARIE CASSART, NICOLAS PETTIAUX, PIERRE ALAIN GEVENOIS, MANUEL PAIVA, MARC ESTENNE
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We have used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm length (Ldi) and surface area (Adi), the length (Ldo) and surface area (Ado) of the dome, and the length (Lap) and surface area (Aap) of the zone of apposition in 10 hyperinflated patients with severe chronic obstructive pulmonary disease, or COPD (FEV1 = 27% predicted: FRC = 225% predicted) and 10 normal subjects matched for age, sex, and height. Measures of Ldi, Adi, Lap, and Aap decreased linearly between FRC and TLC in the two groups, but Ldo and Ado did not change. On average, patients' Adi and Aap at FRC were reduced to 73% and 54% of normal values, whereas Ado was unaffected. When compared at similar absolute lung volumes, mean diaphragm dimensions were similar in patients with COPD and normal subjects, but individual values were very variable in both groups. This variability was partly accounted for by differences in body weight: i.e., the greater the weight, the longer the diaphragm. We conclude that (1) patients with COPD have marked reductions in Adi and Aap at FRC but have diaphragm dimensions similar to those of normal subjects when compared at similar absolute lung volumes, and (2) normal subjects and patients with COPD show substantial intersubject variability in diaphragm dimensions that is partly explained by differences in body weight.
Endoscopy and Audit Free Papers
Authors: S.J. Panter, H. O'Flanagan, M.G. Bramble
Journal: Gut (2001)

Conclusion:No imaging modality consistently predicts the persistence of viable tumour following neo-adjuvant chemotherapy.Consequently, the questions asked of imaging should be (a) is there a high likelihood of residual tumour?and (b) is this resectable?Endoscopic ultrasound provides accurate answers to both these questions.EUS should form part of the pre-operative assessment for oesophageal cancer following neo-adjuvant chemotherapy.
Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients
Authors: Kevin M. Koch, Nandi J. Reddy, Roger B. Cohen, Nancy L. Lewis, Bonnie Whitehead, Kathleen Mackay, Andrew Stead, Andrew P. Beelen, Lionel D. Lewis
Journal: Journal of Clinical Oncology (2009)

This study was conducted to characterize the effect of food on the relative bioavailability of lapatinib.
Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.
Authors: S P Friedrich, B H Lorell, M F Rousseau, W Hayashida, O M Hess, P S Douglas, S Gordon, C S Keighley, C Benedict, H P Krayenbuehl
Journal: Circulation (1994)

BACKGROUND Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P &lt; .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P &lt; .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.
A comparison of three brands of polysulfone membranes.
Authors: N A Hoenich, C Woffindin, A Brennan, P J Cox, J N Matthews, M Goldfinch
Journal: Journal of the American Society of Nephrology (1996)

A prospective clinical crossover study comparing the functional performance and biocompatibility of three brands of polysulfone membranes (Fresenius Polysultone (Fresenius Ag, Bad Homburg, Germany), Polyphen (Minntech Corp., Minneapolis, MN), and Biosulfane (WR Grace Inc., Danvers, MA)) incorporated in ethylene oxide-sterilized dialyzers of comparable surface area (1.3 to 1.35 m2) was undertaken. The clearance of small molecules by each membrane was comparable. Plasma levels of beta 2 microglobulin fell to 49.9% of pretreatment values by 210 min when using the Fresenius Polysulfone membrane, 60.2% with the Polyphen membrane, and 63.1% with the Biosulfane membrane. The reduction achieved by the Fresenius Polysulfone membrane was superior (P = 0.003). The plasma reductions were associated with the recovery of 195 mg beta 2 microglobulin from the dialysate for the Fresenius Polysulfone membrane and 158 mg for the Polyphen membrane, but no beta 2 microglobulin was recovered from the dialysate with the Biosulfane membrane. The dialysate collected with the Fresenius Polysulfone membrane also contained a mean of 6853 mg of total protein, compared with 5490 mg with the Polyphen membrane and 8422 mg with the Biosulfane (P = 0.04) membrane. The neutropenia was slight and independent of membrane brand, as were the changes in C3a des arg and SC5b-9 complement components. The reduction in platelet counts was higher for the Biosulfane membrane than for the other brands (P = 0.003). This study indicates that whereas the polymer base of the membrane is the same, its production and subsequent handling during dialyzer production induce changes that attain statistical significance, most notably in the way that the membrane removes beta 2 microglobulin and interacts with proteins. The differences observed are a consequence of the different alloying polymers used during manufacture and, consequently, the membranes cannot be considered equivalent.