tbuckley/cabot-search huggingface dataset:
Effect of Left Ventricular Hypertension, Ischemia and Vasoactive Drugs on the Myocardial Distribution of Coronary Flow
Authors: THOMAS W. MOIR, DON W. DEBRA
Journal: Circulation Research (1967)

Distribution of coronary flow to the inner and outer layers of the left ventricle of the anesthetized, open chest dog was estimated by the myocardial uptake of 86 Rb chloride infused into the cannulated common left coronary artery. With normal relationship of coronary perfusion pressure and left intra-ventricular pressure, there was no significant underperfusion of the endocardium. When left intraventricular pressure was raised and coronary perfusion pressure was held at levels sufficient to provide normal coronary flow, endocardial distribution remained equal to or slightly greater than that to the epicardium. However, when coronary perfusion pressure was lowered, particularly to levels causing obvious signs of myocardial hypoxia, maintenance of a normal left intraventricular pressure resulted in marked underperfusion of the endocardium. The coronary vasoactive drugs, dipyridamole, norepinephrine, vasopressin, and the β-adrenergic receptor blocking agent, propranolol, increased the flow distribution to the endocardium of both the normotensive and hypertensive left ventricle. It is concluded that the systolic tissue pressure which increases from epicardium to endocardium does not cause significant underperfusion of the endocardium in either the normotensive or hypertensive left ventricle as long as normal coronary perfusion pressure and flow are maintained.
PKB/Akt-Dependent Regulation of Cell Motility
Authors: G. Xue, B. A. Hemmings
Journal: JNCI Journal of the National Cancer Institute (2013)

The prosurvival activity of phosphoinositide 3 kinase (PI3K)/Akt (also known as protein kinase B, PKB) pathway has been investigated in great detail in human physiology and disease. Accumulating evidence is emerging that this signaling axis also actively engages with the migratory process in motile cells, including metastatic cancer cells. Interference with the role of PI3K/Akt–mediated cell motility impairs cellular development and attenuates malignant progression of cancer metastasis. Because metastasis is responsible for 90% of mortality in cancer patients, the acceleration of cancer cell spreading observed in association with hyperactivation of the PI3K pathway, triggered for example by chemotherapy/radiotherapy in the clinic, has heightened awareness of the conflict between "good drugs" and unfavorable effects. Here, we discuss recent studies on PI3K/Akt–regulated cell motility in both physiological and pathological settings, with the aim of a better understanding of how activities of the PI3K/Akt axis initiate and transmit "migratory signals" that stimulate cell movement. We focus in particular on its direct influence on cell migration and invasion, epithelial-mesenchymal transition, and cancer metastasis.
Managing Substance Dependence as a Chronic Disease
Authors: Patrick G. O’Connor
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
BOOP and COP.
Authors: D M Geddes
Journal: Thorax (1991)

BOOP and COP are essentially the same condition and represent one of many ways in which the lung may respond to an inflammatory stimulus. Some underlying causes of BOOP have been identified but in many cases no cause can be found. The clinical and radiological features are of a pneumonic illness that responds to corticosteroids rather than antibiotics, but as milder cases are being identified the clinical spectrum is widening. Most cases can be confidently diagnosed only by open lung biopsy, but bacteriological lavage and transbronchial biopsy followed by a trial of steroids may sometimes be considered.
High-Dose Chemotherapy in the Treatment of Relapsed Osteosarcoma: An Italian Sarcoma Group Study
Authors: F. Fagioli, M. Aglietta, A. Tienghi, S. Ferrari, A. Brach del Prever, E. Vassallo, A. Palmero, E. Biasin, G. Bacci, P. Picci, E. Madon
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To study the feasibility and activity of two courses of high-dose chemotherapy (HDCT) in patients with osteosarcoma in metastatic relapse. PATIENTS AND METHODS: Patients with high-grade osteosarcoma in metastatic relapse (multiple metastases or solitary metastasis at intervals of less than 30 months) were eligible for study. High-dose chemotherapy consisted of carboplatin and etoposide followed by stem-cell rescue. A second course was planned 4 to 6 weeks after the first. Surgery was performed before or after HDCT. RESULTS: Thirty-two patients were enrolled onto the study. At the end of the treatment, 25 patients were in complete remission (CR), six were alive with disease progression, and one died of toxicity. At present, 14 patients are alive with a median survival time of 23 months from study entry: four are in first CR, three are in second CR, and one is in fourth CR. Six patients are alive with disease. Eighteen patients (56%) died: 17 of disease and one of toxicity. Transplantation-related mortality was 3.1%. The relapse or progression disease rate was 84.4%. The 3-year overall survival rate is 20% and the 3-year disease-free survival rate is 12%. CONCLUSION: HDCT combined with surgery is feasible and can induce CR in a large portion of patients. Two points, however, need to be considered: only patients who are chemosensitive to induction treatment can obtain CR after HDCT, and the length of remission is short, because most patients relapse. Thus novel strategies are needed to maintain the remission status or to treat patients who do not respond to induction treatment.
Inhibition of leukotriene B4-induced CD11B/CD18 (Mac-1) expression by BIIL 284, a new long acting LTB4 receptor antagonist, in patients with rheumatoid arthritis
Authors: R Alten
Journal: Annals of the Rheumatic Diseases (2004)

Background: Leukotriene B4 (LTB4) has a key role in the pathophysiology of rheumatoid arthritis (RA). Objective: To investigate the inhibition of ex vivo LTB4-induced Mac-1 (CD11b/CD18) expression in leucocytes of patients with RA by the new oral LTB4 receptor antagonist BIIL 284. Methods: The pharmacokinetics and inhibition of LTB4-induced Mac-1 expression of BIIL 284 were characterised in 26 adult patients with RA who were treated with BIIL 284 25 mg, 150 mg, or placebo given once a day for 14 days according to a double blind, randomised, parallel group design. Results: Tmax of BIIL 315 in plasma (main metabolite and active principle of BIIL 284 in plasma) was achieved about four hours after drug administration, and Cmax,ss and AUC0–6h,ss increased in proportion to the dosage. 100% inhibition of LTB4-induced MAC-1 expression was reached after two hours (150 mg) or four hours (25 mg), showing a statistically significant difference in comparison with placebo (p<0.005). A longlasting dynamic effect was seen consistently even when plasma concentrations declined to very low values 24 hours after administration. Secondary clinical efficacy end points remained unchanged probably owing to the short duration of treatment. Adverse events (AEs) were reported in 12 patients during the study. No serious AEs or laboratory AEs were seen. Conclusions: Both the 25 mg and 150 mg doses of BIIL 284 safely and effectively inhibit Mac-1 expression on neutrophils; thus longer treatment with BIIL 284 may result in clinical benefit for patients with RA.
Antagonism of Vascular Endothelial Growth Factor for Macular Edema Caused by Retinal Vein Occlusions: Two-Year Outcomes
Authors: Peter A. Campochiaro, Gulnar Hafiz, Roomasa Channa, Syed M. Shah, Quan Dong Nguyen, Howard Ying, Diana V. Do, Ingrid Zimmer-Galler, Sharon D. Solomon, Jennifer U. Sung, Beena Syed
Journal: Ophthalmology (2010)
To Drink or Not to Drink? That Is the Question
Authors: Robert A. Kloner, Shereif H. Rezkalla
Journal: Circulation (2007)

Numerous studies have used a J-shaped or U-shaped curve to describe the relationship between alcohol use and total mortality. The nadir of the curves based on recent meta-analysis suggested optimal benefit at approximately half a drink per day. Fewer than 4 drinks per day in men and fewer than 2 per day in women appeared to confer benefit. Reductions in cardiovascular death and nonfatal myocardial infarction were also associated with light to moderate alcohol intake. Although some studies suggested that wine had an advantage over other types of alcoholic beverages, other studies suggested that the type of drink was not important. Heavy drinking was associated with an increase in mortality, hypertension, alcoholic cardiomyopathy, cancer, and cerebrovascular events, including cerebrovascular hemorrhage. Paradoxically, light-to-moderate alcohol use actually reduced the development of heart failure and did not appear to exacerbate it in most patients who had underlying heart failure. Numerous mechanisms have been proposed to explain the benefit that light-to-moderate alcohol intake has on the heart, including an increase of high-density lipoprotein cholesterol, reduction in plasma viscosity and fibrinogen concentration, increase in fibrinolysis, decrease in platelet aggregation, improvement in endothelial function, reduction of inflammation, and promotion of antioxidant effects. Controversy exists on whether alcohol has a direct cardioprotective effect on ischemic myocardium. Studies from our laboratory do not support the concept that alcohol has a direct cardioprotective effect on ischemic/reperfused myocardium. Perhaps the time has come for a prospectively randomized trial to determine whether 1 drink per day (or perhaps 1 drink every other day) reduces mortality and major cardiovascular events.
Determinants of exercise capacity in adult subjects with non-cystic fibrosis bronchiectasis
Authors: Anderson Alves de Camargo, Tatiane Soares Amaral, Samia Zahi Rached, Rodrigo Abensur Athanasio, Fernanda de Cordoba Lanza, Jaksoel Cunha Silva, Alberto Cukier, Frederico Leon Arrabal Fernandes, Celso Ricardo Fernandes Carvalho, Rafael Stelmach, Simone Dal Corso
Journal: European Respiratory Journal (2013)

Introduction: The cardiopulmonary exercise testing (CPET) and shuttle walking test (SWT) have been used to evaluate exercise tolerance in subjects with non-cystic fibrosis bronchiectasis (nCF-BCt). However, the determinants of aerobic capacity (peak VO2) and distance walked in SWT (DSWT) are still unknown in this population. Objective: To evaluate the determinants of peak VO2 and DSWT in adult subjects with nCF-BCt. Methods: Eighty subjects with BCQ (50 women; 44±14 yrs; FEV1: 52±19% pred; fat-free mass index: 17±2 kg/m²; peak VO2: 63±13% pred; DSWT: 52±13% pred). Spirometry, maximum voluntary isometric contraction of the quadriceps femoris (MVIC-QF), and a shuttle walking test (SWT) were performed. Peak VO2 was obtained from CPET on a cycle ergometer. Dyspnea was measured according to the Medical Research Council (MRC) scale, and daily steps (DS) with a pedometer. Results: For peak VO2, a stepwise regression analysis was conducted with 61 patients. FEV1 expressed as % pred (partial R² = 0.46, p
Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: New evidence on the potential therapeutic mechanism
Authors: Claudia O. Zein, Rocio Lopez, Xiaoming Fu, John P. Kirwan, Lisa M. Yerian, Arthur J. McCullough, Stanley L. Hazen, Ariel E. Feldstein
Journal: Hepatology (2012)

Pentoxifylline (PTX) improved the histological features of nonalcoholic steatohepatitis (NASH) in a recent randomized placebo-controlled trial. However, the underlying mechanism responsible for the beneficial effects of PTX in NASH remains unidentified. A key role of lipid oxidation in the pathogenesis and progression of NASH has been established. PTX is known to decrease free-radical-mediated oxidative stress and inhibit lipid oxidation. The primary aim of this study was to evaluate the effects of PTX on levels of lipid oxidation products in patients with NASH. Levels of multiple structurally specific oxidized fatty acids including hydroxy-octadecadienoic acids (HODEs), oxo-octadecadienoic acids (oxoODEs), and hydroxy-eicosatetraenoic acids (HETEs) were quantified by mass spectrometry in plasma obtained at baseline and at study completion in patients who completed 1 year of therapy with PTX or placebo in a randomized controlled trial. Therapy with PTX resulted in significant decreases in 9-HODE and 13-oxoODE, oxidized lipid products of linoleic acid (LA) linked to histological severity in nonalcoholic fatty liver disease. Similarly, PTX therapy was associated with significant decreases in 8-HETE, 9-HETE, and 11-HETE compared to placebo. Statistically significant correlations were demonstrated between the decrease in HODEs and oxoODEs and improved histological scores of fibrosis and between the decrease in HETEs and improved lobular inflammation.
Soy Food Intake and Breast Cancer Survival
Authors: Xiao Ou Shu, Ying Zheng, Hui Cai, Kai Gu, Zhi Chen, Wei Zheng, Wei Lu
Journal: JAMA (2009)

<h3>Context</h3>Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients.<h3>Objective</h3>To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence.<h3>Design, Setting, and Participants</h3>The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information.<h3>Main Outcome Measures</h3>Total mortality and breast cancer recurrence or breast cancer–related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable.<h3>Results</h3>During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen.<h3>Conclusion</h3>Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.
Estimation of post-operative forced expiratory volume by functional respiratory imaging
Authors: Annelies Janssens, Wim Vos, Cedric Van Holsbeke, Paul Van Schil, Ellie Oostveen, Jan De Backer, Laurens Carp, Annemie Snoeckx, Wilfried De Backer, Jan P. van Meerbeeck
Journal: European Respiratory Journal (2014)

Surgical resection is a potential curative therapy for patients with early-stage non-small cell lung cancer (NSCLC). Comorbid chronic obstructive pulmonary disease (COPD) is frequently present in these patients [1], stressing the importance of an accurate estimation of post-operative (po) forced expiratory volume in 1 s (FEV1) [2]. A predicted poFEV1 (PpoFEV1) must be calculated whenever the pre-operative FEV1 or diffusing capacity for carbon monoxide is <80% predicted [3]. The anatomic segment method (ASM) and perfusion scintigraphy (QS) are often used for this prediction [4, 5]. Both are known to underestimate the poFEV1 in a substantial fraction of patients, resulting in the possible exclusion from resection of a borderline operable patient [6, 7]. This stresses the need for a more precise tool to estimate poFEV1. Initial results indicate that FRI might better predict post-operative FEV1; confirmation in a larger trial is needed <http://ow.ly/E395t>
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Authors: Yurii S Aulchenko, Samuli Ripatti, Ida Lindqvist, Dorret Boomsma, Iris M Heid, Peter P Pramstaller, Brenda W J H Penninx, A Cecile J W Janssens, James F Wilson, Tim Spector, Nicholas G Martin, Nancy L Pedersen, Kirsten Ohm Kyvik, Jaakko Kaprio, Albert Hofman, Nelson B Freimer, Marjo-Riitta Jarvelin, Ulf Gyllensten, Harry Campbell, Igor Rudan, Asa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A Hicks, Mario Falchi, Gonneke Willemsen, Jouke-Jan Hottenga, Eco J C de Geus, Grant W Montgomery, John Whitfield, Patrik Magnusson, Juha Saharinen, Markus Perola, Kaisa Silander, Aaron Isaacs, Eric J G Sijbrands, Andre G Uitterlinden, Jacqueline C M Witteman, Ben A Oostra, Paul Elliott, Aimo Ruokonen, Chiara Sabatti, Christian Gieger, Thomas Meitinger, Florian Kronenberg, Angela Döring, H-Erich Wichmann, Johannes H Smit, Mark I McCarthy, Cornelia M van Duijn, Leena Peltonen
Journal: Nature Genetics (2008)
Approaches to improve the diagnosis and management of infertility
Authors: P. Devroey, B.C.J.M. Fauser, K. Diedrich
Journal: Human Reproduction Update (2009)

Recent advances in our understanding of the causes of infertility and of assisted reproductive technology (ART) have led to the development of complex diagnostic tools, prognostic models and treatment options. The Third Evian Annual Reproduction (EVAR) Workshop Meeting was held on 26–27 April 2008 to evaluate evidence supporting current approaches to the diagnosis and management of infertility and to identify areas for future research efforts. Specialist reproductive medicine clinicians and scientists delivered presentations based on published literature and ongoing research on patient work-up, ovarian stimulation and embryo quality assessment during ART. This report is based on the expert presentations and subsequent group discussions and was supplemented with publications from literature searches and the authors' knowledge. It was agreed that single embryo transfer (SET) should be used with increasing frequency in cycles of ART. Continued improvements in cryopreservation techniques, which improve pregnancy rates using supernumerary frozen embryos, are expected to augment the global uptake of SET. Adaptation and personalization of fertility therapy may help to optimize efficacy and safety outcomes for individual patients. Prognostic modelling and personalized management strategies based on individual patient characteristics may prove to represent real progress towards improved treatment. However, at present, there is limited good-quality evidence to support the use of these individualized approaches. Greater quality control and standardization of clinical and laboratory evaluations are required to optimize ART practices and improve individual patient outcomes. Well-designed, good-quality studies are required to drive improvements to the diagnosis and management of ART processes.
Soluble RAGE is deficient in neutrophilic asthma and COPD
Authors: M.B. Sukkar, L.G. Wood, M. Tooze, J.L. Simpson, V.M. McDonald, P.G. Gibson, P.A.B. Wark
Journal: European Respiratory Journal (2011)

The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asthma and chronic obstructive pulmonary disease (COPD). Bronchial lavage fluid from subjects with moderate-to-severe persistent asthma (n=16) or COPD (n=37), or from healthy controls (n=18), was analysed for neutrophils, total sRAGE, endogenous secretory RAGE (esRAGE), HMGB1 and SAA. We also determined systemic levels of sRAGE in a separate group of asthmatic (n=101) and COPD (n=34) subjects. Subjects with neutrophilic asthma or COPD had undetectable levels of lung sRAGE, while levels of sRAGE in asthma/COPD without neutrophilia were similar to those in controls. Systemic sRAGE was significantly decreased in subjects with neutrophilic asthma or COPD compared with those without airway neutrophilia. There was significant positive correlation between total sRAGE and esRAGE in the lung and systemically. HMGB1 levels were similar in all subject groups, while SAA was below detectable levels. Neutrophilic airway inflammation in asthma and COPD is associated with reduced sRAGE.