tbuckley/cabot-search huggingface dataset:
Modification of human atrioventricular nodal function by selective atrioventricular nodal artery catheterization.
Authors: P J Wang, G Sosa-Suarez, P L Friedman
Journal: Circulation (1990)

The hypothesis that human atrioventricular (AV) nodal function can be modulated selectively with a new technique of AV nodal artery catheterization was tested in eight subjects referred for diagnostic cardiac catheterization or electrophysiological studies. Three patients had no history of arrhythmias. Three patients had supraventricular tachycardia (SVT) due to reentry confined to the AV node (AVNRT). One patient had SVT due to reentry over a concealed AV bypass tract (AVRT-CBT), and one patient had nonsustained ventricular tachycardia. In each subject, sinus cycle length, AH interval, HV interval, AV nodal effective refractory period (AVN-ERP), and Wenckebach paced cycle length were measured in a control state. A flexible infusion catheter was then positioned selectively in the AV nodal artery of each subject. Through this catheter, a constant infusion of 0.1 mg/min procainamide at a flow rate of 0.125 ml/min (n = 1) or 50 micrograms/min acetylcholine at a flow rate of 0.25 ml/min (n = 4) was administered. Electrophysiological parameters were determined again during selective AV nodal artery drug infusion and during infusion of saline at identical rates. Two subjects developed transient AV nodal block during selective AV nodal catheterization alone and did not receive an infusion of drug or saline. A stable position of the AV nodal artery catheter could not be achieved in one other subject, who also received no drug or saline. In the other five subjects, drug infusion caused an increase in AVN-ERP from a control value of 312 +/- 52 msec to a value of 543 +/- 228 msec (p less than 0.05) and an increase in Wenckebach paced cycle length from a control value of 360 +/- 47 msec to a value of 572 +/- 217 msec (p less than 0.05). These parameters were unchanged from control during selective saline infusion. In two patients with AVNRT, drug infusion abolished SVT by causing complete blockade of ventriculoatrial conduction as well as lengthening of anterograde AVN-ERP. In the patient with AVRT-CBT, drug infusion abolished SVT by preventing repetitive anterograde AV conduction. Saline had no effect on SVT inducibility. Selective AV nodal artery catheterization enables AV nodal function to be modulated exclusively. Delivery of ablative agents to the AV node by this technique may be useful in patients with refractory SVT.
Neonatal Rash Due to Herpes Gestationis
Authors: Nissa I Erickson, Richard L Ellis
Journal: New England Journal of Medicine (2002)

Figure 1. A 6-day-old infant with a 48-hour history of facial lesions had been born at 37 weeks of gestation after a spontaneous vaginal delivery without complications. According to her mother, the newborn was thriving and had had no behavioral changes coincident with the onset of the rash. Multiple yellow plaques on erythematous bases — some with tiny vesicles — were scattered and at times coalescent across the infant's face, but the periorbital region and mucosa were spared (Panel A). At 33 weeks of gestation, the infant's mother had had an intensely pruritic rash characterized by widely scattered papular and . . .
A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.
Authors: M L Hartman, P E Clayton, M L Johnson, A Celniker, A J Perlman, K G Alberti, M O Thorner
Journal: Journal of Clinical Investigation (1993)

To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions.
Acute megakaryoblastic leukemia in children and adolescents, excluding Down's syndrome: improved outcome with intensified induction treatment
Authors: D Reinhardt, S Diekamp, C Langebrake, J Ritter, J Stary, M Dworzak, A Schrauder, M Zimmermann, G Fleischhack, W-D Ludwig, J Harbott, U Creutzig
Journal: Leukemia (2005)
597 SERUM/ERITROCYTE RIBAVIRIN X 100 RATIO AS AN INDICATOR OF SVR IN HCV GENOTYPE-1 PATIENTS OBTAINING EVR
Authors: L. Baiocchi, F. De Leonardis, M. Delle Monache, L. Nosotti, L.R. Conti, I. Lenci, M. Carbone, A. Salso, M. Angelico
Journal: Journal of Hepatology (2009)
Exercise-induced ST-segment elevation in leads V1 or aVL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease.
Authors: R F Dunn, B Freedman, D T Kelly, I K Bailey, A McLaughlin
Journal: Circulation (1981)

Exercise-induced ST-segment elevation in leads V1 and/or aVL in the absence of anterior Q waves occurred in 46 of 190 patients (24%) who underwent 12-lead exercise electrocardiography with thallium-201 myocardial perfusion imaging and coronary arteriography. Significant left anterior descending coronary artery (LAD) disease was present in 38 of 46 patients (83%) with V1/aVL ST evaluation and in 72 of 144 patients (50%) without V1/aVL ST elevation (p less than 0.0005). Anterior myocardial ischemia, indicated by reversible anterior perfusion defects on thallium scanning, was present in 40 of 46 patients (87%) with V1/aVL ST elevation and in 25 of 144 patients (17%) without V1/aVL ST elevation (p less than 0.0005). Exercise ST elevation in V1/aVL was detected in 38 of 110 of the patients (35%) with LAD disease, for a specificity of 90%, and in 40 of 65 of the patients (62%) with anterior myocardial ischemia, for a specificity of 95%. We conclude that during 12-lead exercise electrocardiography, ST-segment elevation in V1 and/or a VL in the absence of anterior Q waves predicts anterior myocardial ischemia and LAD disease.
A Simplified Method of Assessing Hemodynamics in Technetium-99m Sulfur Colloid Liver Imaging
Authors: EDDY C.K. TONG, YONG-OK SON, CHARLES H.S. LEE
Journal: Clinical Nuclear Medicine (1987)

A total of 204 Tc-99m sulfur colloid hemodynamic studies of the liver taken at 5-second intervals were evaluated. The time when the gradually increasing activity in the liver becomes equal to the reducing activity in the heart pool is defined as the relative half clearance time (RHCT) of cardiac activity to the liver. The RHCT was measured in each scan and was correlated with clinical information, liver function tests, and static scan findings. Normal RHCT was established to be in the range of 40 ± 20 seconds. This study indicates that the RHCT truly reflects the functional status of the hepatic blood flow as well as the phagocytic activity of the Kupffer cells of the liver when cardiac function is normal. A prolonged RHCT may indicate the presence of a parenchymal disease of the liver or cardiac failure with hepatic congestion, or both. The longer the RHCT, the more severe the pathologic condition of the liver, provided that cardiac function is normal.
The Prognostic Value of B-Type Natriuretic Peptide in Patients with Acute Coronary Syndromes
Authors: James A. de Lemos, David A. Morrow, Jane H. Bentley, Torbjørn Omland, Marc S. Sabatine, Carolyn H. McCabe, Christian Hall, Christopher P. Cannon, Eugene Braunwald
Journal: New England Journal of Medicine (2001)

Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation.We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study.The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months.A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.
17-Hydroxy-jolkinolide B Inhibits Signal Transducers and Activators of Transcription 3 Signaling by Covalently Cross-Linking Janus Kinases and Induces Apoptosis of Human Cancer Cells
Authors: Ying Wang, Xiuquan Ma, Shousheng Yan, Shensi Shen, Huiling Zhu, Yuan Gu, Hongbing Wang, Guowei Qin, Qiang Yu
Journal: Cancer Research (2009)

Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs frequently in cancer cells and contributes to oncogenesis. Among the members of STAT family, STAT3 plays a pivotal role in the development and progression of human tumors. The STAT3-mediated signaling pathway has been recognized as a promising anticancer target. Here, we show that 17-Hydroxy-jolkinolide B (HJB), a diterpenoid from the Chinese medicinal herb Euphorbia fischeriana Steud, strongly inhibits interleukin (IL)-6-induced as well as constitutive STAT3 activation. Furthermore, we show that HJB directly targets the JAK family kinases, JAK1, JAK2, and TYK2, by inducing dimerization of the JAKs via cross-linking. Addition of DTT or glutathione prevents the JAK cross-linking and blocks the inhibitory effects of HJB on IL-6-induced STAT3 activation, suggesting that HJB may react with cystein residues of JAKs to form covalent bonds that inactivate JAKs. Liquid chromatography/mass spectrometry analysis confirmed that each HJB reacted with two thiols. The effect of HJB on the JAK/STAT3 pathway is specific as HJB has no effect on platelet-derived growth factor, epidermal growth factor, or insulin-like growth factor I signaling pathways. Finally, we show that HJB inhibits growth and induces apoptosis of tumor cells, particularly those tumor cells with constitutively activated STAT3. We propose that the natural compound HJB is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor.
Oxygen Saturation and Outcomes in Preterm Infants
Authors: Ben J. Stenson, William O. Tarnow-Mordi, Brian A. Darlow, John Simes, Edmund Juszczak, Lisa Askie, Malcolm Battin, Ursula Bowler, Roland Broadbent, Pamela Cairns, Peter Graham Davis, Sanjeev Deshpande, Mark Donoghoe, Lex Doyle, Brian W. Fleck, Alpana Ghadge, Wendy Hague, Henry L. Halliday, Michael Hewson, Andrew King, Adrienne Kirby, Neil Marlow, Michael Meyer, Colin Morley, Karen Simmer, Win Tin, Stephen P. Wardle, Peter Brocklehurst
Journal: New England Journal of Medicine (2013)

The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used.
An Experience With Artificial Sweeteners
Authors: Edwin Boros
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Packets containing calcium saccharine and calcium cyclamate are popular as a substitute for sugar, and are widely used in low-calory soft drinks. The Food and Drug Administration has announced the safety of these chemicals for popular consumption. The following experience records the adverse effects that these combined chemicals induced in this writer. My past history reflects an absence of medical problems, with the exception of the usual affections of infancy and early childhood, and frequent sieges of coryza, pharyngitis, and sinusitis requiring occasional treatment with tetracycline, erythromycin, demethylchlortetracycline (Declomycin), salicylates, and antihistamines. All medications have been well tolerated without sign of allergy. An operation 8 years ago for a benign rectal polyp and a tonsillectomy 40 years ago were the only surgical requirements. From time to time, small daily doses of thyroid extract have been ingested as an adjuvant to weight reduction. About a year ago, I
People in deprived areas of England are less likely to survive cancer
Authors: O. Mashta
Journal: BMJ (2008)

People living in the most deprived areas of England are even less likely to survive common cancers than previously believed, new figures published by the Office for National Statistics indicate.

The largest differences between people living in deprived areas and the rest of England are in cancers of the bladder and rectum, the figures show.

Researchers from the Office for National Statistics and the London School of Hygiene and Tropical Medicine analysed data from patients who were given diagnoses of seven common cancers during 1998 to 2003. They compared cancer survival among people living in “spearhead” …
Sodium–hydrogen exchange inhibition attenuates glycoside-induced hypertrophy in rat ventricular myocytes
Authors: Xiaohong Tracey Gan, Xiang-Qun Gong, Jenny Xue, James V. Haist, Donglin Bai, Morris Karmazyn
Journal: Cardiovascular Research (2009)

Cardiac glycosides induce cardiomyocyte hypertrophy via yet to be defined mechanisms. These hypertrophic effects are likely related to changes in intracellular signalling secondary to Na+-K+ ATPase (NKA) inhibition which would produce elevations in intracellular sodium concentrations. Sodium–hydrogen exchanger isoform 1 (NHE-1) also contributes to intracellular sodium regulation. Accordingly, we determined the contribution of NHE-1 to cardiac glycoside-induced hypertrophy. The majority of the experiments were performed on cultured neonatal rat ventricular myocytes exposed to either ouabain (100 µM) or digoxin (40 µM) for 24 h, although additional experiments were also done using adult left ventricular myocytes with 30 µM of either glycoside. Both glycosides increased cell surface area by 30% and atrial natriuretic peptide gene expression by two- to three-fold (P < 0.05 for both). These effects were associated with a significant reduction in the expression of two NKA isoforms, α2 and α3, whereas the α1 isoform was unaffected. Conversely, both glycosides increased NHE-1 expression in cardiomyocytes by approximately two-fold and significantly increased intracellular sodium concentrations by more than 60% (P < 0.05). Both ouabain and digoxin were also found to significantly increase phosphorylation of mitogen-activated protein kinases. All these effect were prevented when identical experiments were carried out in the presence of the NHE-1 inhibitors EMD 87580 or AVE 4890. Identical results were obtained using adult myocytes, although this was associated with downregulation of all three NKA isoforms. Glycoside-induced increase in cell shortening or intracellular Ca2+ transients was not significantly affected by NHE-1 inhibition. When taken together, these studies show that NHE-1 inhibition attenuates the hypertrophic effect of cardiac glycosides without affecting inotropic parameters and suggest a possible approach to limiting glycoside-induced hypertrophic responses while preserving therapeutic, i.e. inotropic, actions.
Accidental Separation of the Placenta at the Seventh Month of Pregnancy: Alarming Syncope: Induction of Premature Labour: Recovery
Authors: G. E. Stanger
Journal: BMJ (1861)

they may formii an opinion ou the galvano-caustic moode of operating, I will finally state mny own conviction, that it is only in exceptional cases that the galvano- caustic apparatus slhould be substitute(d for either caus- tics (were it not for the cumbersomiietness of the appa- ratus, it should always suipersede the common actual cautery), the ecraseutr, or cutting instruments.Hence, I would not advise every practisiuga suirgeon to possess himself of the instruments; but, since these excep- tional cases not unfiequently occur, I would have each surgeon aware of this mode of operating; and in eaclh large district there shiouldl be an operator possessed of the apparatus, to whom application could be made, in a case whiere this plan of operating was indicated.Before the introduction of the ecraseur, the galvano- caustic mode of operatin, was imore required than now; and it is probable that our haviin heard so little of it recently in England, may depenid on the employment at present of the ecraseuzr by those who otherwise would have used the galvanic apparatus.
Chronic Activation of Wild-Type Epidermal Growth Factor Receptor and Loss of Cdkn2a Cause Mouse Glioblastoma Formation
Authors: Jaime Acquaviva, Hyun Jung Jun, Julie Lessard, Rolando Ruiz, Haihao Zhu, Melissa Donovan, Steve Woolfenden, Abraham Boskovitz, Ami Raval, Roderick T. Bronson, Rolf Pfannl, Charles A. Whittaker, David E. Housman, Al Charest
Journal: Cancer Research (2011)

Glioblastoma multiforme (GBM) is characterized by overexpression of epidermal growth factor receptor (EGFR) and loss of the tumor suppressors Ink4a/Arf. Efforts at modeling GBM using wild-type EGFR in mice have proven unsuccessful. Here, we present a unique mouse model of wild-type EGFR-driven gliomagenesis. We used a combination of somatic conditional overexpression and ligand-mediated chronic activation of EGFR in cooperation with Ink4a/Arf loss in the central nervous system of adult mice to generate tumors with the histopathologic and molecular characteristics of human GBMs. Sustained, ligand-mediated activation of EGFR was necessary for gliomagenesis, functionally substantiating the clinical observation that EGFR-positive GBMs from patients express EGFR ligands. To gain a better understanding of the clinically disappointing EGFR-targeted therapies for GBM, we investigated the molecular responses to EGFR tyrosine kinase inhibitor (TKI) treatment in this model. Gefitinib treatment of primary GBM cells resulted in a robust apoptotic response, partially conveyed by mitogen-activated protein kinase (MAPK) signaling attenuation and accompanied by BIM(EL) expression. In human GBMs, loss-of-function mutations in the tumor suppressor PTEN are a common occurrence. Elimination of PTEN expression in GBM cells posttumor formation did not confer resistance to TKI treatment, showing that PTEN status in our model is not predictive. Together, these findings offer important mechanistic insights into the genetic determinants of EGFR gliomagenesis and sensitivity to TKIs and provide a robust discovery platform to better understand the molecular events that are associated with predictive markers of TKI therapy.
Ultrasonographic "soft markers" of fetal chromosomal defects
Authors: M. Whittle
Journal: BMJ (1997)

The promise of cloning for human medicineNot a moral threat but an exciting challenge T he production of a sheep clone, Dolly, from an adult somatic cell 1 is a stunning achievement of British science.It also holds great promise for human medicine.Sadly, the media have sensationalised the implications, ignoring the huge potential of this experiment.Accusations that scientists have been working secretively and without the chance for public debate are invalid.Successful cloning was publicised in 1975, 2 and it is over eight years since Prather et al published details of the first piglet clone after nuclear transfer. 3issing from much of the debate about Dolly is recognition that she is not an identical clone.Part of our genetic material comes from the mitochondria in the cytoplasm of the egg.In Dolly's case only the nuclear DNA was transferred.Moreover, we are a product of our nurture as much as our genetic nature.Monovular twins are genetically closer than are artificially produced clones, and no one could deny that such twins have quite separate identities.Dolly's birth provokes fascinating questions.How old is she?Her nuclear DNA gives her potentially adult status, but her mitochondria are those of a newborn.Mitochrondia are important in the aging process because aging is related to acquired mutations in mitochondrial DNA, possibly caused by oxygen damage during an individual's life. 4Experimental nuclear transfer in animals and in human cell lines could help elucidate mechanisms for many of these processes.Equally extraordinary is the question concerning the role of the egg's cytoplasm in mammalian development.Once the quiescent nucleus had been transferred to the recipient egg cell, developmental genes expressed only in very early life were switched on.There are likely to be powerful factors in the cytoplasm of the egg that make this happen.Egg cytoplasm is perhaps the new royal jelly.Studying why and how these genes switch on would give important information about both human development and genetic disease.Research on nuclear transfer into human eggs has immense clinical value.Here is a model for learning more about somatic cell differentiation.If, in due course, we could influence differentiation to give rise to targeted cell types we might generate many tissues of great value in transplantation.These could include skin and blood cells, and possibly neuronal tissue, for the treatment of injury, for bone marrow transplants for leukaemia, and for degenerative diseases such as Parkinson's disease.One problem to be overcome is