tbuckley/cabot-search huggingface dataset:
Simvastatin Preserves the Ischemic-Reperfused Myocardium in Normocholesterolemic Rat Hearts
Authors: Allan M. Lefer, Barry Campbell, Yong-Kyoo Shin, Rosario Scalia, Reid Hayward, David J. Lefer
Journal: Circulation (1999)

Background —Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as cardiomyocyte injury. These deleterious effects are due in large part to endothelial dysfunction leading to the upregulation of cell adhesion molecules and subsequent neutrophil-endothelium interaction. At clinically relevant doses, simvastatin, an HMG-CoA reductase inhibitor, has been shown to lower serum cholesterol levels and normalize endothelial cell function. We wanted to test the effects of simvastatin on neutrophil-mediated cardiac dysfunction in a controlled model of myocardial ischemia-reperfusion. Methods and Results —This study examines the effects of simvastatin in a neutrophil-dependent isolated perfused rat heart model of ischemia (I) (20 minutes) and reperfusion (R) (45 minutes) injury. Administration of simvastatin 25 μg/rat improved coronary flow and preserved left ventricular developed pressure (LVDP) and dP/dt max , indexes of cardiac contractile function. Final LVDP was 95±5 mm Hg in I/R hearts perfused with PMNs and simvastatin, compared with 49±4 mm Hg in PMN-perfused I/R hearts receiving only vehicle ( P &lt;0.001). In addition, simvastatin significantly reduced PMN accumulation in the ischemic myocardium ( P &lt;0.01). In PMN-perfused rat hearts after I/R, simvastatin also significantly attenuated P-selectin expression, CD18 upregulation in rat PMNs, and PMN adherence to rat vascular endothelium. Significant, although less potent, effects were obtained with pravastatin. Conclusions —These results provide evidence that HMG-CoA reductase inhibitors are potent and effective cardioprotective agents that inhibit leukocyte–endothelial cell interactions and preserve cardiac contractile function and coronary perfusion after myocardial ischemia and reperfusion. Moreover, these effects are unrelated to the cholesterol-lowering action of this agent and appear to be mediated by enhanced endothelial release of NO.
An Administrative Claims Model Suitable for Profiling Hospital Performance Based on 30-Day Mortality Rates Among Patients With an Acute Myocardial Infarction
Authors: Harlan M. Krumholz, Yun Wang, Jennifer A. Mattera, Yongfei Wang, Lein Fang Han, Melvin J. Ingber, Sheila Roman, Sharon-Lise T. Normand
Journal: Circulation (2006)

Background— A model using administrative claims data that is suitable for profiling hospital performance for acute myocardial infarction would be useful in quality assessment and improvement efforts. We sought to develop a hierarchical regression model using Medicare claims data that produces hospital risk-standardized 30-day mortality rates and to validate the hospital estimates against those derived from a medical record model. Methods and Results— For hospital estimates derived from claims data, we developed a derivation model using 140 120 cases discharged from 4664 hospitals in 1998. For the comparison of models from claims data and medical record data, we used the Cooperative Cardiovascular Project database. To determine the stability of the model over time, we used annual Medicare cohorts discharged in 1995, 1997, and 1999–2001. The final model included 27 variables and had an area under the receiver operating characteristic curve of 0.71. In a comparison of the risk-standardized hospital mortality rates from the claims model with those of the medical record model, the correlation coefficient was 0.90 (SE=0.003). The slope of the weighted regression line was 0.95 (SE=0.007), and the intercept was 0.008 (SE=0.001), both indicating strong agreement of the hospital estimates between the 2 data sources. The median difference between the claims-based hospital risk-standardized mortality rates and the chart-based rates was &lt;0.001 (25th and 75th percentiles, −0.003 and 0.003). The performance of the model was stable over time. Conclusions— This administrative claims-based model for profiling hospitals performs consistently over several years and produces estimates of risk-standardized mortality that are good surrogates for estimates from a medical record model.
Myocardial Injury and Cardiac Troponin I Release After Off-Pump Versus On-Pump Coronary Surgery
Authors: Carol Chen-Scarabelli, Tiziano M. Scarabelli
Journal: Circulation (2004)

In a recent study by Selvanayagam and colleagues aimed at evaluating reversible and irreversible myocardial injury in patients undergoing off-pump (OP-) versus on-pump (P-) coronary artery bypass surgery (CABG), 1 the authors documented a similar incidence and magnitude of new irreversible myocardial injury in both groups, despite the greater release of cardiac troponin I (cTnI) after P-CABG.These findings raise questions about not only the clinical significance of increased cTnI levels after P-CABG, but also the higher degree of cardioprotection allegedly supplied by OP-CABG.The extent of cTnI release does not necessarily correlate with occurrence or magnitude of irrevocable myocardial injury.Although the inaccuracy of cTnI levels in the "quantification" of postsurgical myocardial infarction seems to be mainly related to the "washout phenomenon," the lack of correlation between cTnI release and occurrence of irreversible myocardial injury may be ascribed to iatrogenic stressors, intrinsic to the P-CABG surgical approach, and not typically associated with enduring myocardial injury.Release of cTnI after P-CABG was detected in bypass patients in the absence of ischemic conditions, 2 as well as associated with myocardial stunning 3 (a common occurrence after P-CABG), and elevated preload, independently of cardiac ischemia. 4 This release, potentially occurring in cardiopulmonary bypass together with that inevitably associated with surgical manipulations, may possibly explain higher, though benign, cTnI levels, detected in P-CABG versus OP-CABG.Reperfusion, whether pharmacologically or mechanically achieved, results in earlier and augmented cTnI release versus no reperfusion.This was substantiated by a recent study showing that P-CABG had graft patency rates significantly greater than OP-CABG, despite higher cTnI levels at 6 to 12 hours postoperatively. 5 Additional studies are therefore needed to confirm whether an earlier and greater cTnI release in P-CABG patients should be paradoxically welcomed as a marker of earlier and greater reperfusion.
Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut
Authors: Grace Lu-Yao, Peter C Albertsen, Janet L Stanford, Therese A Stukel, Elizabeth S Walker-Corkery, Michael J Barry
Journal: BMJ (2002)

To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut.Natural experiment comparing two fixed cohorts from 1987 to 1997.Seattle-Puget Sound and Connecticut surveillance, epidemiology, and end results areas.Population based cohorts of male Medicare beneficiaries aged 65-79 drawn from the Seattle (n=94 900) and Connecticut (n=120 621) areas.Rates of screening for prostate cancer, treatment with radical prostatectomy and external beam radiotherapy, and prostate cancer specific mortality.The prostate specific antigen testing rate in Seattle was 5.39 (95% confidence interval 4.76 to 6.11) times that of Connecticut, and the prostate biopsy rate was 2.20 (1.81 to 2.68) times that of Connecticut during 1987-90. The 10 year cumulative incidences of radical prostatectomy and external beam radiotherapy up to 1996 were 2.7% and 3.9% for Seattle cohort members compared with 0.5% and 3.1% for Connecticut cohort members. The adjusted rate ratio of prostate cancer mortality up to 1997 was 1.03 (0.95 to 1.11) in Seattle compared with Connecticut.More intensive screening for prostate cancer and treatment with radical prostatectomy and external beam radiotherapy among Medicare beneficiaries in the Seattle area than in the Connecticut area was not associated with lower prostate cancer specific mortality over 11 years of follow up.
Oral contraceptives are drug of choice for menorrhagia in the Netherlands
Authors: S. Zwart, L. J Meijer
Journal: BMJ (1997)

Editor–John Bonnar and Brian L Sheppard studied, in an academic setting, only 81 patients selected from a population of over 400 (referred?) patients complaining of heavy menstruation.1 Unfortunately, they supply insufficient information to make general practitioners reconsider their policy on treating menorrhagia. We are members of a …
EXCESSIVE MYOPIA: WHEN MAY WE OPERATE AND WHAT MAY WE EXPECT?
Authors: ANDREW TIMBERMAN
Journal: JAMA (1899)

Just one decade ago, Fukala called the ophthalmic surgeons of the world from the safe retreat of surgical conservatism, into which they had been so effectually scared thirty years previously by the disastrous experience of Mooren. He presented to the Wiener Medicinische Gesellschaft, two cases of excessive myopia on which he had successfully operated. But Lister had come and dispelled the shadows of sepsis, in which Mooren had probably done his work. Fukala, made brave by the experience of the preceding few years, worked in an entirely different light. The difference between Mooren and Fukala was the difference between sepsis and asepsis, and in no surgical work is the difference, as gauged by practical results, greater than in ophthalmic surgery. The past ten years have contributed much to the elaboration of our knowledge concerning excessive myopia and its surgical treatment. Extravagant claims by enthusiasts and the lay press on the
Deficient Neurogenesis in Forebrain-Specific Presenilin-1 Knockout Mice Is Associated with Reduced Clearance of Hippocampal Memory Traces
Authors: Ruiben Feng, Claire Rampon, Ya-Ping Tang, David Shrom, Janice Jin, Maureen Kyin, Bryce Sopher, George M Martin, Seong-Hun Kim, Ronald B Langdon, Sangram S Sisodia, Joe Z Tsien
Journal: Neuron (2001)
Applied Respiratory Physiology: With Special Reference to Anesthesia
Authors: David W. Cugell
Journal: JAMA (1970)

This is a marvelous textbook of respiratory physiology. I disagree with the author on only one point— the title. The word applied should be deemphasized or deleted. Further, it will be regrettable if the subtitle With Special Reference to Anesthesia dissuades those in other disciplines from realizing the benefit and enjoyment this splendid volume provides.  Dr. Nunn is a distinguished anesthesiologist in Great Britain with extensive experience in clinical anesthesiology and physiological research. In this volume he presents a detailed review of human respiratory physiology, commencing with a brief consideration of the physics of gases, and then covering control of breathing, both chemical and neural, respiratory mechanics, ventilation, distribution of both air and blood within the lung, pulmonary circulation, gas transfer, and the chemistry of carbon dioxide and oxygen. A particularly valuable feature of this text is the many illustrations—primarily simplified line drawings—charts, and nomograms. The figures have lengthy legends.
Preventive Effects of Heregulin-β <sub>1</sub> on Macrophage Foam Cell Formation and Atherosclerosis
Authors: Gang Xu, Takuya Watanabe, Yoshitaka Iso, Shinji Koba, Tetsuo Sakai, Masaharu Nagashima, Shigeko Arita, Shigeki Hongo, Hidekazu Ota, Youichi Kobayashi, Akira Miyazaki, Tsutomu Hirano
Journal: Circulation Research (2009)

Rationale : Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. Objective : The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. Methods and Results : Plasma heregulin-β 1 levels were significantly decreased in 31 patients with acute coronary syndrome and 33 patients with effort angina pectoris compared with 34 patients with mild hypertension and 40 healthy volunteers (1.3±0.3, 2.0±0.4 versus 7.6±1.4, 8.2±1.2 ng/mL; P &lt;0.01). Among all patients with acute coronary syndrome and effort angina pectoris, plasma heregulin-β 1 levels were further decreased in accordance with the severity of coronary artery lesions. Expression of heregulin-β 1 was observed at trace levels in intracoronary atherothrombosis obtained by aspiration thrombectomy from acute coronary syndrome patients. Heregulin-β 1 , but not heregulin-α, significantly reduced acetylated low-density lipoprotein–induced cholesterol ester accumulation in primary cultured human monocyte-derived macrophages by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-β 1 significantly decreased endocytic uptake of [ 125 I]acetylated low-density lipoprotein and ACAT activity, and increased cholesterol efflux to apolipoprotein (Apo)A-I from human macrophages. Chronic infusion of heregulin-β 1 into ApoE −/− mice significantly suppressed the development of atherosclerotic lesions. Conclusions : This study provided the first evidence that heregulin-β 1 inhibits atherogenesis and suppresses macrophage foam cell formation via SR-A and ACAT1 downregulation and ABCA1 upregulation.
Proliferative characteristics of monoblasts grown in vitro.
Authors: T J Goud, R van Furth
Journal: The Journal of Experimental Medicine (1975)

In a previous study also done with a liquid culture technique, the monoblast was identified and characterized as the most immature cell of the mononuclear phagocyte cell line recognized so far. The present study concerned the proliferative behavior of the monoblast and promonocyte in colonies. The cell-cycle times of both cell types were determined on the basis of four independent methods. The resulting values all show excellent agreement: for the monoblast 11.0-11.9 h, and for the promonocyte 11.4-12.8 h. The DNA-synthesis time found for the two cell types amounted to 5.7 h for the monoblast and 5.5 h for the promonocyte. The duration of the other phages of the cell cycle of the proliferating mononuclear phagocytes proved to be: G2 phase, 0.6 h; mitosis phage, 1.8 h; and G1 phase, 3.5-3.8 h. The individual colonies showed a biphasic pattern of colony growth, an initial phase of rapid proliferation being followed by a stage wtih a markedly decreased growth rate. In the initial stage only monoblasts are present in the colony; when the growth rate slows down promonocytes and macrophages appear. These observations support the earlier conclusion that the monoblast is without doubt the precursor of the promonycyte. Colony size was found to vary widely. The main factor underlying this variation proved to be the lag time between the start of the culture and the time point at which the colony-forming cells begin to divide. Mathematical analysis showed that the variation in colony size probably does not arise from heterogeneity of the population of colony-forming cells. A mathematical approach was used to determine the proportion of self-replicating and differentiating cells among the dividing monoblasts and promonocytes in the colony. The results indicate that initially in vitro the majority of the cells of both types are self-replicating cells, but later an increasing proportion of the dividing cells give rise to another, more mature type of cell. On the basis of the conclusion that the monoblast initiates the mononuclear phagocyte colony, the number of monoblasts (2.5 X 10(5)) present in vivo was estimated to be half the number of the promonocytes. In view of this ratio the mostly likely pattern for the proliferation of mononuclear phagocytes in the bone marrow is that a monoblast divides once, giving rise to two promonocytes which in their turn divide once and form two nonproliferating monocytes.
Paradoxical bronchoconstriction and salmeterol.
Authors: B. H. Davies
Journal: BMJ (1992)

although opioids have their own clinically relevant adverse effects.'There is much current interest in the use of non-steroidal anti-inflammatory drugs as adjuvant agents with other analgesics after surgery.Several studies have shown that combining non-steroidal anti-inflammatory drugs with opioids provides superior analgesia with less total opioid required and possibly a reduction in side effects mediated by opioids, such as respiratorv depression and sedation.Furthermore, there is good reason to believe that giving non-steroidal anti-inflammatory drugs before surgery may result in a pre-emptive analgesic effect with a subsequent reduction in postoperative analgesic requirements and the associated adverse effects.'The results of controlled trials to substantiate this effect in humans are awaited.We suggest, therefore, that until there is stronger evidence for clinically significant impairment of wound healing, non- steroidal anti-inflammatory drugs should continue to be used for surgical patients without other contraindications as they have a useful role in the management of postoperative pain.
Impaired biliary excretion and whole body elimination of methylmercury in rats with a congenital defect in biliary glutathione excretion
Authors: Nazzareno Ballatori, Zenaida Gatmaitan, Anh T. Truong
Journal: Hepatology (1995)

Biliary excretion of methylmercury, a major route of elimination of this toxic compound, was less than 2% of control in Eisai hyperbilirubinemic (EHBR) rats, a mutant Sprague-Dawley strain with a defect in biliary excretion of a variety of organic anions, including glutathione S-conjugates and reduced glutathione (GSH). Biliary GSH excretion in EHBR rats was also < 2% of controls, confirming previous findings. Impaired biliary methylmercury and GSH excretion was not explained by decreased hepatic content of these compounds. Indeed, hepatic methylmercury and GSH concentrations in EHBR rats were actually double those of controls. To assess the significance of the impaired biliary excretion in the whole body elimination of the toxicant, 203Hg excretion was measured over a 17-day period after intraperitoneal administration of either 0.5 or 5 mumol/kg of 203Hg-methylmercury chloride. The results for the two doses were similar. Methylmercury was eliminated by a first order process; however, the biological half-line was significantly longer in the EHBR rats, 46 to 54 days versus 18 to 22 days. Fecal excretion was the main route of elimination in both control and mutant animals. At necropsy (17 days), 16% to 25% of the 203Hg dose was recovered in the liver of the EHBR rats, whereas livers of control animals contained less than 2%of the administered dose. These findings demonstrate the biliary excretion of methylmercury is markedly impaired in EHBR rats and is associated with a low biliary GSH excretion, providing support for the hypothesis that methylmercury is normally transported across the canalicular membrane by a GSH-dependent mechanism, and presumably as a GSH mercaptide (CH3Hg-SG).(ABSTRACT TRUNCATED AT 250 WORDS)
Self-control as habit
Authors: Max Hocutt
Journal: Behavioral and Brain Sciences (1995)

Abstract Self-control has traditionally been explained in the terms of faculty psychology, as the exercise of free will or the use of reason in choosing between different individual acts. Rachlin explains self-control behavioristically, as the preference for habits over individual acts. His explanation resolves the paradoxes faced by the others and has the additional advantage of being verifiable.
Smallpox bioterrorist conference highlights divisions over vaccines
Authors: F. Fleck
Journal: BMJ (2003)

Several international experts who met in Geneva this week warned that a bioterrorist attack using smallpox was not only possible but probable. They urged governments to prepare themselves before it was too late.

But their message was somewhat undermined by the fact that the conference, entitled “Smallpox BioSecurity,” was initiated and financed by Acambis, a US company that manufactures vaccine.

The conference was also being held only a week after US federal health officials proclaimed that the US smallpox vaccination programme was over.

“The fact is, it's ceased,” Ray Strikas of the Centers for Disease Control and Prevention (CDC), told USA Today (16 October, p A 01). No one had issued an edict to say stop, but the pace of new vaccinations had dropped dramatically in April after well publicised reports of unexpected heart problems, he said. At its peak, hundreds of health workers were vaccinated, …
Persistence Of IgE Anti-influenza Virus Antibodies In Pediatric And Adult Serum Post Vaccination With Influenza Virus Vaccine
Authors: D. Wong, M. Kusonruksa, K.B. Norowitz, R. Joks, H.G. Durkin, M.H. Bluth, T.A. Smith-Norowitz
Journal: Journal of Allergy and Clinical Immunology (2011)
Higher energy synchronized external direct current cardioversion for refractory atrial fibrillation
Authors: Walid Saliba, Nour Juratli, Mina K Chung, Mark J Niebauer, Okan Erdogan, Richard Trohman, Bruce L Wilkoff, Ralph Augostini, Kent A Mowrey, George R Nadzam, Patrick J Tchou
Journal: Journal of the American College of Cardiology (1999)
Nineteenth Annual Pezcoller Symposium: Hypothesis-Driven Clinical Investigation in Cancer
Authors: William G. Kaelin, Charles L. Sawyers, Enrico Mihich
Journal: Cancer Research (2007)

This symposium was held in Trento, Italy, from June 14 to 16, 2007, and was co chaired by William G. Kaelin, Enrico Mihich, and Charles L. Sawyers. A session was devoted to the proof of concept derived from successes in target-oriented therapeutics. Molecular targets must be identified in each patients because they are equally present in all patients with the same tumor type. A session was devoted to the identification of markers of drug effectiveness. Two sessions were focused on opportunities for developing new specific molecular target-oriented therapies.