tbuckley/cabot-search huggingface dataset:
Extended Survival and Prognostic Factors for Patients With <i>ALK</i>-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Authors: Kimberly L. Johung, Norman Yeh, Neil B. Desai, Terence M. Williams, Tim Lautenschlaeger, Nils D. Arvold, Matthew S. Ning, Albert Attia, Christine M. Lovly, Sarah Goldberg, Kathryn Beal, James B. Yu, Brian D. Kavanagh, Veronica L. Chiang, D. Ross Camidge, Joseph N. Contessa
Journal: Journal of Clinical Oncology (2015)

We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis.A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling.Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001).Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.
GE-06 * PROGNOSTIC SIGNIFICANCE OF RELATIVE 1p19q CODELETION IN OLIGODENDROGLIAL TUMORS
Authors: M. Chamberlain
Journal: Neuro-Oncology (2014)

BACKGROUND: 1p19q codeletion is a favorable prognostic marker for oligodendroglial tumors (OT) that in anaplastic OT is as well predictive of good response to radiotherapy and alkylator chemotherapy. OBJECTIVE: Assess outcome in relative 1p19q codeleted OT defined as the presence of both polysomy and 1p19q codeletion. METHODS: Between the years 2001-2013, 525 cases were examined at the University of Washington by dual color FISH for 1p or 19q deletion. 437 (82%) were WHO Grade 2 or 3 OT of which 209 (48%) were 1p19q codeleted. 72 (16%) were relatively deleted for either one or both 1p and 19q of which 28 (6%) were relatively 1p19q codeleted. RESULTS: Median overall survival was as follows. WHO Grade 2 OT (n = 296): 1p19q codeleted (n = 155) 13+ years; uni- or nondeleted (n = 86) 5+ years; relative deletion for one or both 1p19q (n = 41)) 6+ years; and relative 1p19q codeletion (n = 15) 6+ years. WHO Grade 3 OT (n = 168): 1p19q codeleted (n = 54) 11+ years; uni- or nondeleted (n = 70) 2.5 years; relative deletion for one or both 1p19q (n = 31)) 3 years; and relative 1p19q codeletion (n = 13) 4+ years. CONCLUSIONS: Median overall survival for OT either WHO Grade 2 or 3 with relative codeletion of 1p19q were approximately one half that of 1p19q codeleted tumors. The presence of relative codeletion, operationally defined as polysomy with deletions, is of prognostic significance.
The kallikrein-kinin system and prostaglandins in the kidney: their relation to forosemide-induced diuresis and to the renin-angiotensin-aldosterone system in man.
Authors: K Abe, N Irokawa, M Yasujima, M Seino, S Chiba, Y Sakurai, K Yoshinaga, T Saito
Journal: Circulation Research (1978)

The relations among the renin-angiotensin-aldosterone system, renal prostaglandin E, the renal kallikrein-kinin system, and furosemide diuresis were studied in 16 healthy volunteers.The diuretic and natriuretic effects of furosemide were accompanied by an increase in the excretion rates of urinary prostaglandin E (UPCEV), urinary kallikrein (UkaiiV), and urinary kinin (U k i n i n V), and in plasma renin activity (PRA) and plasma aldosterone concentration (PAC).However, the time courses of the increase in PRA and PAC following furosemide administration and assumption of an upright posture were different from those of UPCEV, UkaiiV, UkininV, urine flow (UV), and urinary sodium output (UNBV).In comparison with the early increase in UPCEV, UkaiiV, UkininV, UV and UN O V, the increases in PRA and PAC were delayed.The augmentation of UPGEV, UkaiiV, and UkininV was closely related to the diuretic and natriuretic effects of furosemide.Highly significant correlations also were found between UPGE V and Ukaii V, UPGE V and Ukinin V, and Ukaii V and UkininV.On the contrary, there were no significant correlations between UPCEV and PRA or PAC, between Ukaii V and PRA or PAC, or between UkininV and PRA or PAC before and after the furosemide injection.These results indicate that the augmentation of urinary prostaglandin E and urinary kallikrein-kinin system following furosemide administration is independent of the renin-angiotensin-aldosterone system but directly dependent on the effects of furosemide.The possibility that renal prostaglandin E and the renal kallikrein-kinin system are involved in the diuretic and natriuretic effects of furosemide also is suggested by these experiments.
Diabetes Mellitus Impairs Vasodilation to Hypoxia in Human Coronary Arterioles
Authors: Hiroto Miura, Ruth E. Wachtel, Fausto R. Loberiza, Takashi Saito, Mamoru Miura, Alfred C. Nicolosi, David D. Gutterman
Journal: Circulation Research (2003)

ATP-sensitive K + channels (K ATP ) contribute to vasomotor regulation in some species. It is not fully understood the extent to which K ATP participate in regulating vasomotor tone under physiological and pathophysiological conditions in the human heart. Arterioles dissected from right atrial appendage were studied with video microscopy, membrane potential recordings, reverse transcription–polymerase chain reaction, and immunohistochemistry. Hypoxia produced endothelium-independent vasodilation and membrane hyperpolarization of vascular smooth muscle cells, both of which were attenuated by glibenclamide. Aprikalim, a selective K ATP opener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription–polymerase chain reaction detected mRNA expression for K ATP subunits, and immunohistochemistry confirmed the localization of the inwardly rectifying Kir6.1 protein in the vasculature. In patients with type 1 or type 2 diabetes mellitus (DM), vasodilation was reduced to both aprikalim (maximum dilation, DM(+) 90±2% versus DM(−) 96±1%, P &lt;0.05) and hypoxia (maximum dilation, DM(+) 56±8% versus DM(−) 85±5%, P &lt;0.01) but was not altered to sodium nitroprusside or bradykinin. Baseline myogenic tone and resting membrane potential were not affected by DM. We conclude that DM impairs human coronary arteriolar dilation to K ATP opening, leading to reduced dilation to hypoxia. This reduction in K ATP function could contribute to the greater cardiovascular mortality and morbidity in DM.
External Cooling Applied to Febrile Patients with Septic Shock: Control for Cointerventions?
Authors: Daniel J. Niven, Kevin B. Laupland, H. Tom Stelfox
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

It is with great interest that we read the multicenter, randomized “Sepsiscool” clinical trial by Schortgen and colleagues investigating the effects of external cooling among febrile patients with septic shock (1). This clinical trial adds further evidence to the growing efforts to define an evidence-based approach to fever control in critically ill patients. They found that external cooling with a cooling blanket or cold bed sheets and ice packs was strongly associated with (1) a decrease in the dose of vasopressor required to maintain a mean arterial pressure of at least 65 mm Hg at 12 and 24 hours after randomization; and (2) a decrease in early (14-d) mortality in febrile patients with septic shock.
Cardiac and peripheral actions of growth hormone and its releasing peptides: Relevance for the treatment of cardiomyopathies
Authors: S MARLEAU, M MULUMBA, D LAMONTAGNE, H ONG
Journal: Cardiovascular Research (2005)

Ischemic and nonischemic cardiomyopathies are associated with significant morbidity and mortality in industrialized countries. Cardiomyopathies of primary origin, and more specifically the dilated form of the disease, have been associated with a number of gene defects in cytoskeletal, membrane, and sarcomeric proteins. Cardiomyopathies of secondary origin such as ischemic cardiomyopathy remain the leading cause of left ventricular systolic dysfunction and heart failure. Among novel strategies to improve cardiac function in heart failure, treatment with growth hormone, insulin growth factor-1 (IGF-1), and natural and synthetic growth hormone-releasing peptides such as ghrelin and hexarelin have been explored. The present review focuses on the issues involved in the use of exogenous growth hormone and its releasing peptides in experimental animal models of chronic heart failure and in clinical studies on cardiomyopathic patients as potential releasing peptides for the treatment of chronic heart failure developing as a consequence of cardiomyopathy.
Cigarette Smoking Acutely Increases Platelet Thrombus Formation in Patients With Coronary Artery Disease Taking Aspirin
Authors: Joseph Hung, Jules Y.T. Lam, Lucie Lacoste, Glaci Letchacovski
Journal: Circulation (1995)

Background Smoking is associated with an increased risk of myocardial infarction and sudden death. Platelet activation and thrombosis at sites of vessel stenosis and injury or plaque disruption play a crucial role in these acute coronary events. Thus, the aim of this study was to determine whether cigarette smoking acutely increases platelet thrombus formation on an injured arterial surface at local shear rates typical of a stenotic artery. Methods and Results Twelve habitual smokers with stable coronary disease, on aspirin 325 mg/d, were studied immediately before and 5 minutes after smoking two cigarettes each. Ex vivo platelet thrombus formation on porcine arterial media (simulating deep arterial injury) was measured after exposure to the patient’s circulating venous blood for 3 minutes in cylindrical flow chambers at 37°C. The flow chambers were designed to produce shear rates of 754 or 2546 s −1 , the latter being typical of the high shear rates produced by vessel stenosis. Plasma catecholamine, thromboxane B 2 , and 6-ketoprostaglandin F 1α (6-keto-PGF 1α ) levels and whole blood platelet aggregation responses to thrombin were also measured before and after smoking. Compared with before smoking, morphometrically measured platelet thrombus formation on arterial media at shear rates of 754 and 2546 s −1 increased by an average of 48% ( P =.19) and 64% ( P =.014), respectively, after smoking. Plasma epinephrine increased by more than twofold after smoking ( P =.026). Plasma thromboxane B 2 and 6-keto-PGF 1α levels did not change. Smoking also increased whole blood platelet aggregation to thrombin ( P ≤.05). Conclusions These results suggest that smoking-enhanced platelet thrombosis may be an important contributory mechanism for acute coronary events in smokers that is not prevented by aspirin treatment. Catecholamine release and heightened platelet aggregation response to in vivo agonists may contribute to the prothrombotic effects of smoking.
Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases
Authors: W. Jeffrey Allard, Jeri Matera, M. Craig Miller, Madeline Repollet, Mark C. Connelly, Chandra Rao, Arjan G. J. Tibbe, Jonathan W. Uhr, Leon W. M. M. Terstappen
Journal: Clinical Cancer Research (2004)

The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas.The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors.Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers.The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
HCC-1, a novel chemokine from human plasma.
Authors: P Schulz-Knappe, H J Mägert, B Dewald, M Meyer, Y Cetin, M Kubbies, J Tomeczkowski, K Kirchhoff, M Raida, K Adermann, A Kist, M Reinecke, R Sillard, A Pardigol, M Uguccioni, M Baggiolini, W G Forssmann
Journal: The Journal of Experimental Medicine (1996)

A novel CC chemokine, HCC-1, was isolated from the hemofiltrate of patients with chronic renal failure. HCC-1 has a relative molecular mass of 8,673 and consists of 74 amino acids including four cysteines linked to disulfide bonds. HCC-1 cDNA was cloned from human bone marrow and shown to code for the mature protein plus a putative 19-residue leader sequence. Mature HCC-1 has sequence identity of 46% with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and 29-37% with the other human CC chemokines. Unlike MIP-1 alpha and the other CC chemokines, HCC-1 is expressed constitutively in several normal tissues (spleen, liver, skeletal and heart muscle, gut, and bone marrow), and is present at high concentrations (1-80 nM) in plasma. HCC-1 has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induced intracellular Ca2+ changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and was inactive on T lymphocytes, neutrophils, and eosinophil leukocytes. In addition, HCC-1 enhanced the proliferation of CD34+ myeloid progenitor cells. It was as effective as MIP-1 alpha, but about 100-fold less potent.
Effect of funding source on publication bias is not so clear cut
Authors: M. van Lent, H. J. Out
Journal: BMJ (2013)

We agree with Jones and colleagues that non-publication of trial results is unethical, unnecessarily exposing research subjects to the risks and burdens of trial participation.1

The authors report that non-publication was more common in trials that received industry funding (150/468; 32%) than in those that did not (21/117; …
Constitutive Cardiac Overexpression of Sarcoplasmic/Endoplasmic Reticulum Ca <sup>2+</sup> -ATPase Delays Myocardial Failure After Myocardial Infarction in Rats at a Cost of Increased Acute Arrhythmias
Authors: Ying Chen, Brigitte Escoubet, Fabrice Prunier, Julien Amour, Warner S. Simonides, Benoît Vivien, Christophe Lenoir, Michèle Heimburger, Christine Choqueux, Barnabas Gellen, Bruno Riou, Jean-Baptiste Michel, Wolfgang M. Franz, Jean-Jacques Mercadier
Journal: Circulation (2004)

Heart failure often complicates myocardial infarction (MI), and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) is underexpressed in the failing myocardium. We examined the effect of preexisting cardiac SERCA2a protein overexpression on rat survival and left ventricular (LV) remodeling after MI.Baseline myocardial SERCA2a expression was 37% higher in transgenic (TG) rats than in their wild-type (WT) controls, consistent with enhanced myocardial function. The mortality rate of TG rats during the 24 hours after surgical MI was higher than that of WT rats (71% versus 35%, P<0.001), associated with a higher frequency of ventricular arrhythmias, and was normalized by lidocaine treatment. The increased acute-phase mortality in TG rats was not accompanied by increased 6-month mortality. Function of the noninfarcted myocardium, as assessed by tissue Doppler imaging, was higher in TG rats than in WT rats for up to 1 month after MI, a beneficial effect no longer observed at 3 months. LV remodeling and global function were similar in TG and WT rats. No difference in papillary muscle function was found at 6 months.Constitutive cardiac SERCA2a overexpression has a transient beneficial effect on remote myocardium function in rat MI, with no improvement in LV global function or prevention of LV remodeling and failure. This benefit is associated with a higher risk of acute mortality, which is prevented by lidocaine treatment.
A British Medical Association Lecture. ON LUMBO-SACRAL BACKACHE
Authors: P. J. Verrall
Journal: BMJ (1924)

t ZRI JOURNNAM~~~~~~~~~~~~~~ that he has cut the hepatic artery.It is worth remembering that the surface of the liver, stripped by the removal of a simiple mucocele, will often bleed more freely than after the removal of an infected gall bladder.When the detachmienlt exposes a wide area of the liver, bile sometimes leaks from small bilo ducts thus damaged, sometimies so freely for twenty-four hours or more as to raise the suspicion that the ligature has slipped off the cystic duct.COMPLICATIONS OF CHOLFCYSTECTO3MY.An important complication of calculous cholccvstitis is fistulous union of the gall bladder anid colon d(ue to ulcer-a- tion and escape of gall stones illto the gut.A gall stonie
Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia
Authors: Stefan O. Ciurea, Mei-Jie Zhang, Andrea A. Bacigalupo, Asad Bashey, Frederick R. Appelbaum, Omar S. Aljitawi, Philippe Armand, Joseph H. Antin, Junfang Chen, Steven M. Devine, Daniel H. Fowler, Leo Luznik, Ryotaro Nakamura, Paul V. O’Donnell, Miguel-Angel Perales, Sai Ravi Pingali, David L. Porter, Marcie R. Riches, Olle T. H. Ringdén, Vanderson Rocha, Ravi Vij, Daniel J. Weisdorf, Richard E. Champlin, Mary M. Horowitz, Ephraim J. Fuchs, Mary Eapen
Journal: Blood (2015)
Pulmonary and cardiac beta-adrenoceptor density in vivo in asthmatic subjects.
Authors: F Qing, S U Rahman, C G Rhodes, M J Hayes, S Sriskandan, P W Ind, T Jones, J M Hughes
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To examine whether there is a primary deficit in beta-adrenoceptor density in asthma, pulmonary and cardiac beta-receptor density was determined in vivo with positron emission tomography (PET) in 10 male asthmatic subjects (36 +/- 8 yr of age) and compared with that in 30 age-matched normal male subjects (36 +/- 8 yr of age). Pulmonary beta-receptor density was 10.3 +/- 1.8 pmol/g tissue for the asthmatic group and 10.9 +/- 1.9 for the normal group. Cardiac beta-receptor density was 9.1 +/- 3.3 pmol/g for the asthmatic group and 8.8 +/- 2.3 pmol/g for the normal group. There was no difference in either pulmonary or cardiac beta-receptor density between the two groups. In addition, an inverse relationship was observed between FEV1 % predicted and pulmonary beta-receptor density in asthmatic subjects. In conclusion, beta-receptor numbers are normal in untreated asthmatic subjects.
Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling
Authors: Mariona Nadal-Ribelles, Núria Conde, Oscar Flores, Juan González-Vallinas, Eduardo Eyras, Modesto Orozco, Eulàlia de Nadal, Francesc Posas
Journal: Genome biology (2012)

Abstract Background Cells are subjected to dramatic changes of gene expression upon environmental changes. Stress causes a general down-regulation of gene expression together with the induction of a set of stress-responsive genes. The p38-related stress-activated protein kinase Hog1 is an important regulator of transcription upon osmostress in yeast. Results Genome-wide localization studies of RNA polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in RNA Pol II localization, with a shift toward stress-responsive genes relative to housekeeping genes. RNA Pol II relocalization required Hog1, which was also localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1 also localized to RNA polymerase III-bound genes, pointing to a wider role for Hog1 in transcriptional control than initially expected. Interestingly, an increasing association of Hog1 with stress-responsive genes was strongly correlated with chromatin remodeling and increased gene expression. Remarkably, MNase-Seq analysis showed that although chromatin structure was not significantly altered at a genome-wide level in response to stress, there was pronounced chromatin remodeling for those genes that displayed Hog1 association. Conclusion Hog1 serves to bypass the general down-regulation of gene expression that occurs in response to osmostress, and does so both by targeting RNA Pol II machinery and by inducing chromatin remodeling at stress-responsive loci.