tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Epoetin Alfa in Critically Ill Patients
Authors: Howard L. Corwin, Andrew Gettinger, Timothy C. Fabian, Addison May, Ronald G. Pearl, Stephen Heard, Robert An, Peter J. Bowers, Paul Burton, Mark A. Klausner, Michael J. Corwin
Journal: New England Journal of Medicine (2007)

Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions.In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov].).
A MODIFICATION IN TRACHEOTOMY
Authors: H. G. B. Russell
Journal: BMJ (1930)

TWn TiltTTnE 594 OCT.I IC, 19301 --, bfit~~~~~~~~~~~~~~~~~~MDZCAL-JOUNAw deposited, and, sinco tiho muscles retract, ossification may occur above the patella, for two or three inches.Subse- (plent x-ray examinations 'show gradual condensation cf a b cFrG. 5.-Casc of avulsion of the quadriceps trcated conservatively by imiimobilization of the kuiee on a back splint.a, One day after injury.b, Four weeks after injury.c, Two years after injury.Despite immobilization, the quadriceps has retracted an(l its lower two inclhes is ossified.Better results follow immediate operative repair.
Notch1 Expression, Which Is Related to p65 Status, Is an Independent Predictor of Prognosis in Colorectal Cancer
Authors: Dake Chu, Yi Zhou, Zixi Zhang, Yuming Li, Jipeng Li, Jianyong Zheng, Hongwei Zhang, Qingchuan Zhao, Weizhong Wang, Rui'an Wang, Gang Ji
Journal: Clinical Cancer Research (2011)

Notch1 has been proven to be aberrantly expressed in colorectal cancer and related to tumor differentiation status. However, few previous studies concentrated on the predictive role of Notch1 expression on the overall survival of patients with colorectal cancer. This study explored expression of Notch1 and its relationship with p65 and prognosis in colorectal cancer.Two independent study cohorts were involved in the present study. Clinical specimens from 941 eligible patients were constructed into tissue microarrays. The expression of Notch1 and p65 protein was investigated by immunohistochemistry.Statistically significant positive correlations were found between protein expression of Notch1 and p65 in both retrospective and prospective study cohorts. Patients with higher Notch1 expression showed a trend of having shorter survival time, whereas patients with lower Notch1 expression had better survival in both study cohorts. In multivariate analysis, Notch1 expression was proven to be an independent predictor of prognosis. Moreover, the prognostic value of Notch1 might differ according to p65 status.Notch1 is an independent predictor of prognosis for patients with colorectal cancer. In addition, the predictive role of Notch1 on clinical outcome might be modified by p65 status, suggesting that targeting Notch1 and nuclear factor κB (NF-κB) might be a promising strategy for colorectal cancer treatment.
Leukocyte Reduction in Blood Component Therapy
Authors: T A Lane, K C Anderson, L T Goodnough, S Kurtz, G Moroff, P T Pisciotto, M Sayers, L E Silberstein
Journal: Annals of Internal Medicine (1992)

▪ Purpose: To review methods of preventing or minimizing the adverse effects associated with the transfusion of passenger leukocytes present in cellular blood components and to define groups of patients who are at risk for adverse effects. ▪ Data Sources: English-language articles on transfusion medicine. ▪ Study Selection: Original reports describing the pathogenesis of leukocyte-induced adverse effects in transfusion recipients and the influence of leukocytereduced blood components on these effects. ▪ Data Extraction: Evaluation of the diagnosis, transfusion history, and treatment of the study patients; the methods and results of leukocyte reduction; and specific outcomes, including development of alloimmunization to leukocytes, febrile reactions to transfusion, and platelet refractoriness. ▪ Data Synthesis: Passenger leukocytes are the chief cause of alloimmunization to human leukocyte antigen (HLA) and leukocyte-specific antigens in transfusion recipients. Alloimmunization may result in febrile transfusion reactions, platelet refractoriness, and acute lung injury. Leukocytes are also the vector for transfusionassociated cytomegalovirus infection. Technologic advances in the leukocyte reduction of cellular blood components have made it possible to reduce the number of leukocytes to fewer than 107 per transfusion. Findings suggest that the use of leukocyte-reduced cellular blood components may minimize or prevent recurrent febrile reactions and alloimmunization to leukocyte antigens. Cytomegalovirus may not be transmitted by blood components containing fewer than 107 leukocytes. ▪ Conclusions: Leukocyte reduction in red blood cell and platelet transfusions using third-generation filters is indicated for selected patients who are likely to receive long-term transfusion support, to prevent recurrent febrile reactions and to prevent or delay alloimmunization to leukocyte antigens. Leukocyte-depleted transfusions may also be indicated to delay or prevent refractoriness to platelet transfusion.
Comparison of the immune response to Epstein-Barr virus and cytomegalovirus in sera and synovial fluids of patients with rheumatoid arthritis.
Authors: M Musiani, M Zerbini, S Ferri, M Plazzi, G Gentilomi, M La Placa
Journal: Annals of the Rheumatic Diseases (1987)

The immune response against two herpesviruses has been determined in sera and matched synovial fluids of patients with rheumatoid arthritis (RA) and compared with that of a healthy control population. The increased level of antibody to Epstein-Barr virus (EBV) induced antigens in patients with RA resembles the antibody pattern observed against cytomegalovirus (CMV) induced antigens, which suggests the presence of a pathological condition in patients with RA that can reactivate latent viral infections. The antibody response against EBV and CMV observed in synovial fluids excludes the local production of specific antibodies against EBV and CMV antigens.
Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic Acid
Authors: John W. Eikelboom, Graeme J. Hankey, Jim Thom, Deepak L. Bhatt, P. Gabriel Steg, Gilles Montalescot, S. Claiborne Johnston, Steven R. Steinhubl, Koon-Hou Mak, J. Donald Easton, Christian Hamm, Tingfei Hu, Keith A.A. Fox, Eric J. Topol
Journal: Circulation (2008)

Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B(2) concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B(2) concentrations that could thereby reduce cardiovascular risk.Urinary 11-dehydro thromboxane B(2) concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B(2) concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P=0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B(2), whereas aspirin dose > or =150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B(2) levels.In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B(2) are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events.
Serum Potassium and Clinical Outcomes in the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)
Authors: Bertram Pitt, George Bakris, Luis M. Ruilope, Lorenzo DiCarlo, Robin Mukherjee
Journal: Circulation (2008)

Aldosterone blockade is recommended for patients with congestive heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction; however, the perceived risk of hyperkalemia may limit implementation of this therapeutic approach. This subanalysis examined the relationship between eplerenone, serum potassium (K(+)), and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS).Hospitalized patients with congestive heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction (left ventricular ejection fraction < or =40%) treated with standard therapy were randomized 3 to 14 days after the acute myocardial infarction to additional treatment with eplerenone (25 to 50 mg/d; n=3319) or placebo (n=3313). Patients were excluded if baseline K(+) was >5.0 mEq/L or serum creatinine was >2.5 mg/dL. In patients receiving standard therapy, the addition of eplerenone resulted in a 4.4% absolute increase in the incidence of K(+) >5.5 mEq/L, a 1.6% increase of K(+) > or =6.0 mEq/L, and a 4.7% absolute decrease in hypokalemia (K(+) <3.5 mEq/L). Four independent baseline predictors of hyperkalemia (defined as > or =6.0 mEq/L) were identified: potassium (K(+) greater than the median; 4.3 mEq/L), estimated glomerular filtration rate (< or =60 mL . min(-1) . 1.73 m(-2)), history of diabetes mellitus, and prior use of antiarrhythmic agents. None of these independent baseline risk factors significantly impacted the cardiovascular benefit of eplerenone for reducing all-cause mortality.Use of selective aldosterone blockade with eplerenone within the dose range of 25 to 50 mg/d in post-acute myocardial infarction patients with heart failure and left ventricular systolic dysfunction who are treated with standard therapy improves outcomes without an excess of risk of hyperkalemia (> or =6.0 mEq/L) when periodic monitoring of serum K(+) is instituted.
Calcium current depression in isolated human atrial myocytes after cessation of chronic treatment with calcium antagonists.
Authors: B Le Grand, S Hatem, E Deroubaix, J P Couetil, E Coraboeuf
Journal: Circulation Research (1991)

The present study investigates the possibility that the slow calcium current of human atrial cardiac cells is modified by chronic treatment (1-24 months) with calcium antagonists (nifedipine, nicardipine, or diltiazem) in a manner different from a simple drug-induced blocking effect. Data from treated patients were recorded approximately 30 hours after cessation of the treatment and were compared with those of nontreated patients. In the treated group, the action potential plateau of atrial fibers was always markedly and irreversibly depressed, and action potential duration measured at 50% repolarization was markedly shortened (81 +/- 12 msec, n = 13) compared with normal values (155 +/- 9 msec, n = 28). In isolated atrial cells, peak calcium current density at +10 mV in treated cells was more than three times as small as that in nontreated cells. Steady-state inactivation relations of calcium current as a function of membrane potential were not significantly different in treated and nontreated cells. In contrast, in treated and nontreated cells superfused with 10(-6) M nifedipine, the curves were markedly shifted toward negative potentials. Cell superfusion with 10(-6) M Bay K 8644 increased calcium current to a larger extent in nontreated cells (sixfold increase) than in treated cells (threefold increase), whereas a 23-fold increase was observed in nontreated cells in which the current had been previously depressed by superfusion with 10(-6) M nifedipine. In contrast to Bay K 8644, 10(-7) M isoproterenol and 10(-8) M angiotensin II increased the calcium current to the same extent in both treated and nontreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Polymorphonuclear neutrophil function in systemic sclerosis.
Authors: L Czirják, K Dankó, S Sipka, M Zeher, G Szegedi
Journal: Annals of the Rheumatic Diseases (1987)

In vitro functions of polymorphonuclear (PMN) neutrophils were studied in 20 patients with progressive systemic sclerosis (PSS). An increase in the basal chemiluminescence (CL) activity of peripheral blood PMNs was found, suggesting that these cells had been preactivated in vivo. Patients with more extensive skin disease or signs of disease progression tended to have higher basal CL values. Active oxygen products during the respiratory burst may increase the extent of inflammatory and fibrotic processes and could be involved in the endothelial injury in PSS. The stimulatory capacity of CL response was normal in our study. No alterations were found in the opsonised yeast phagocytic activity of granulocytes when compared with control values. The binding of erythrocyte-antibody particles was found also to be normal. A depressed chemotactic activity of PMN cells against zymosan activated serum was also shown. The cause of the decreased chemotaxis of PMNs remains to be elucidated.
Evaluating hypoxia during air travel in healthy infants: Table 1
Authors: Mansi Khanna, Claire Shackleton, Maureen Verheggen, Mary Sharp, Andrew C Wilson, Graham L Hall
Journal: Thorax (2013)

Up to a third of ex-preterm infants flying near term exhibit pulse oxygen saturation (SpO<sub>2</sub>) of less than 85% during air travel. A hypoxia challenge test (HCT) is recommended to evaluate the requirement for in-flight supplemental O<sub>2</sub>. The validity of the HCT in healthy, term infants has not been reported. This study aimed to characterise the in-flight hypoxia response and the accuracy of the HCT to predict this response in healthy, term infants in the first year of life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel during which parents monitored SpO<sub>2</sub>. Thirty-two flights were undertaken with six infants completing multiple flights. The median in-flight SpO<sub>2</sub> nadir was 87% and significantly lower than the HCT SpO<sub>2</sub> nadir (92%: p&lt;0.001). Infants on seven flights recorded SpO<sub>2</sub>&lt;85% with one infant recording a HCT with a SpO<sub>2</sub> less than 85%. There was marked variability in the in-flight SpO<sub>2</sub> in the six infants who undertook multiple flights, and for three of these infants, the SpO<sub>2</sub> nadir was both above and below 85%. We report that in healthy term infants an in-flight SpO<sub>2</sub> below 85% is common and can vary considerably between flights and that the HCT poorly predicts the risk of in-flight hypoxia (SpO<sub>2</sub>&lt;85%). As it is common for healthy term infants to have SpO<sub>2</sub> less than 85% during air travel further research is needed to clarify whether this is an appropriate cut-off in this age group.
Who undertakes the consultations in the outpatient department?
Authors: R S Kiff, P A Sykes
Journal: BMJ (1988)

In a study of all 4275 outpatient consultations over one month in a district general hospital it was found that the clinics in surgical specialties had the largest numbers of patients. In general surgery less than half of new patients and only one third of all patients attending the clinic were seen by a consultant. (Nine months later about a third of all new patients had still not seen a consultant in the clinic.) In the medical clinics just over a quarter of patients were seen by doctors who had less than six months' experience in their present specialty after registration. Overall, doctors had been on continuous duty for at least 24 hours before a third of consultations. Doctors in training had actually worked during the previous night before attending a quarter of the clinics. Much of the large volume of work is performed by tired, incompletely trained doctors. It is suggested that a greater proportion of the work should be performed by fully trained staff. The workload might be reduced by modifying the pattern of the consultation.
Non-linear relationship between lung cancer risk and cigarette tar yield
Authors: H E Davies
Journal: Thorax (2004)

▴ Harris JE, Thun MJ, Mondul AM, et al . Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982–8. BMJ2004;328:72–6 [OpenUrl][1][Abstract/FREE Full Text][2] This study was undertaken to determine the risk of lung cancer associated with medium, low, and very low tar filter cigarettes. Using a cohort of patients from the US cancer prevention study II (CPS-II), 364 239 men (100 868 current smokers) and 576 535 women … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DHarris%26rft.auinit1%253DJ.%2BE%26rft.volume%253D328%26rft.issue%253D7431%26rft.spage%253D72%26rft.atitle%253DCigarette%2Btar%2Byields%2Bin%2Brelation%2Bto%2Bmortality%2Bfrom%2Blung%2Bcancer%2Bin%2Bthe%2Bcancer%2Bprevention%2Bstudy%2BII%2Bprospective%2Bcohort%252C%2B1982-8%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.37936.585382.44%26rft_id%253Dinfo%253Apmid%252F14715602%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=328/7431/72&atom=%2Fthoraxjnl%2F59%2F4%2F354.atom
Regulation of murine cardiac contractility by activation of α1A-adrenergic receptor-operated Ca2+ entry
Authors: Marion C. Mohl, Siiri E. Iismaa, Xiao-Hui Xiao, Oliver Friedrich, Soeren Wagner, Vesna Nikolova-Krstevski, Jianxin Wu, Ze-Yan Yu, Michael Feneley, Diane Fatkin, David G. Allen, Robert M. Graham
Journal: Cardiovascular Research (2011)

AimsSympathetic regulation of cardiac contractility is mediated in part by α1-adrenergic receptors (ARs), and the α1A-subtype has been implicated in the pathogenesis of cardiac hypertrophy. However, little is known about α1A-AR signalling pathways in ventricular myocardium. The aim of this study was to determine the signalling pathway that mediates α1A-AR-coupled cardiac contractility.
Ischemic Preconditioning Upregulates Vascular Endothelial Growth Factor mRNA Expression and Neovascularization via Nuclear Translocation of Protein Kinase C ε in the Rat Ischemic Myocardium
Authors: Hiroyuki Kawata, Ken-ichi Yoshida, Atsuhiko Kawamoto, Hideyuki Kurioka, Eiji Takase, Yasunobu Sasaki, Kazuhito Hatanaka, Masahiko Kobayashi, Takashi Ueyama, Toshio Hashimoto, Kazuhiro Dohi
Journal: Circulation Research (2001)

Abstract —Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCε was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCε, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCε in the infarcted myocardium.