tbuckley/cabot-search huggingface dataset:
Epidural anaesthesia does not cause long term backache
Authors: F Reynolds, R Russell
Journal: BMJ (1998)

Sensitivity and specificity can both improve as more investigations are usedEditor-We wish to reply to Davie and McMurray's comments about our article on the assessment of acutely dyspnoeic patients with suspected heart failure; we did not see it before publication. 1We too were surprised by the excellent sensitivity of clinical examination in our study.We suspect that all our patients with systolic dysfunction had advanced disease and that assessment by general practitioners before admission resulted in referral of only those with New York Heart Association grade III or IV heart failure.Davie and McMurray criticise the sensitivities obtained when combinations of investigations were used in addition to clinical examination.The apparent misunderstanding relates to the fact that we used clinical examination and/or the various investigations (chest radiography, electrocardiography) in the detection of systolic dysfunction.The left hand column in table 2 in our paper shows the collection of investigations that were used to reach the diagnosis in each case, but the final diagnosis was based on the appropriate abnormality on clinical examination and chest radiography or electrocardiography.This is why sensitivity and specificity can both improve as more investigations are considered.We apologise if this was unclear from our table 2.
Interpreting “Google Flu Trends” data for pandemic H1N1 influenza: The New Zealand experience
Authors: N Wilson, K Mason, M Tobias, M Peacey, Q S Huang, M Baker
Journal: Eurosurveillance (2009)

For the period of the spread of pandemic H1N1 influenza in New Zealand during 2009, we compared results from Google Flu Trends with data from existing surveillance systems. The patterns from Google Flu Trends were closely aligned with (peaking a week before and a week after) two independent national surveillance systems for influenza-like illness (ILI) cases. It was much less congruent with (delayed by three weeks) data from ILI-related calls to a national free-phone Healthline and with media coverage of pandemic influenza. Some patterns were unique to Google Flu Trends and may not have reflected the actual ILI burden in the community. Overall, Google Flu Trends appears to provide a useful free surveillance system but it should probably be seen as supplementary rather than as an alternative.
Abstract 2963: 5-hydroxymethylcytosine alterations at H3K9me3 marked genomic regions serve as potential biomarker for renal cell carcinoma patients
Authors: Wei Meng, Tim Lautenschlaeger, David Frankhouser, Zhenqing Ye, Alexander Huebner, Victor Jin, Pearlly Yan, Arnab Chakravarti
Journal: Cancer Research (2015)

Abstract Background: Epigenetic alterations are frequently encountered in many malignancies. Control of DNA methylation is thought to play a critical role in the global epigenetic reprogramming observed during development and carcinogenesis. DNA demethylation is initiated by the transition from 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). While 5mC patterns are relatively well characterized in many malignancies, not much is known about 5hmC patterns and the potential usefulness as biomarkers. We thus sought out to identify 5hmC alterations in renal cell carcinoma (RCC) and assess their potential usefulness as urine biomarkers. Results: We performed genome-wide 5hmC MethylCap-seq on one pooled RCC tissue sample (n = 3) and the corresponding pooled matched normal kidney tissue (n = 3), as well as on one pooled urine sample obtained from RCC patients (n = 52) and one pooled urine sample obtained from control patients without malignancy (n = 65). Global 5hmC levels were dramatically reduced in RCC tissues compared to matched normal adjacent kidney tissues, and in urine samples compared to tissue samples. Assessing histone marked regions we found 5hmC levels to be highly enriched in H3K9me3 marked repressive genomic regions of RCC tissue compared to normal adjacent tissues. Given the low 5hmC signal in these regions in normal tissues, this difference was also clearly identified comparing urine samples from RCC patients to control patients without RCC. Conclusions: We characterized the 5hmC distribution of RCC and normal human renal tissue as well as of urine samples from RCC patients and control patients without RCC. We identified dramatic genome-wide 5hmC changes to occur during carcinogenesis, which have potential for development as non-invasive urine biomarkers. Citation Format: Wei Meng, Tim Lautenschlaeger, David Frankhouser, Zhenqing Ye, Alexander Huebner, Victor Jin, Pearlly Yan, Arnab Chakravarti. 5-hydroxymethylcytosine alterations at H3K9me3 marked genomic regions serve as potential biomarker for renal cell carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2963. doi:10.1158/1538-7445.AM2015-2963
Ventilatory support
Authors: Gordon Christie, Graeme P Currie, Paul Plant
Journal: BMJ (2006)

Non-invasive ventilationThe introduction and widespread use of non-invasive ventilation (NIV) has revolutionised the management and survival of patients with an acidotic exacerbation of chronic obstructive pulmonary disease (COPD).Indeed, it is difficult to justify admitting patients with an exacerbation of COPD to hospitals where NIV is not readily available.A close fitting facemask or nose mask connected to a portable ventilator facilitates a non-invasive method of providing respiratory support to a spontaneously breathing patient.The mask can be removed easily, allowing patients to communicate, eat, drink, and take nebulised and oral drugs. How non-invasive ventilation worksNIV provides a two level form of respiratory support, supplying inspiratory and expiratory positive airways pressure.Inspiratory positive airways pressure, which is usually titrated up to 15-20 cm H 2 O, helps offload tiring respiratory muscles and reduce the work of breathing, improves alveolar ventilation and oxygenation, and increases elimination of CO 2 .Expiratory positive airways pressure, usually at 4-6 cm H 2 O, helps "splint open" the airway and flushes CO 2 from the mask.It also reduces the work of breathing by overcoming intrinsic positive end expiratory pressure, thereby reducing atelectasis and increasing the end tidal volume.Oxygen is introduced either through a port in the facemask or through a more proximal channel in the ventilator system.It is not usually necessary to deliver humidified oxygen, but humidifiers can be added to the circuit.
Analysis of REIC/Dkk-3 expression in esophageal epithelial cells and esophageal cancers
Authors: Munenori Takaoka, Yuji Kashiwakura, Masami Watanabe, Kazuhiko Ochiai, Masakiyo Sakaguchi, Toshio Nishikawa, Hitoshi Nagatsuka, Yasutomo Nasu, Yoshio Naomoto, Hiromi Kumon
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

912 

[Introduction] The Dickkopf (Dkk) gene family has been suggested to prevent Wnt signaling, leading to suppression of pleiotropic effects in critical biological contexts including development, cell growth/differentiation, and cancer. Although the four genes of the Dkk family known to exist in humans have not been fully characterized, they probably play important functions as well. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers and demonstrated its function as a tumor suppressor gene. Adenovirus-mediated forced expression of REIC/Dkk-3 induced apoptosis through activation of c-Jun-NH2-kinase (JNK). In this study, we analyzed expression status of REIC/Dkk-3 in clinical tissues as well as cultured cells, and determined antiproliferative effect of forced expression of the gene.    [Materials and Methods] Primary esophageal epithelial (EE) cells (KOB-9N, -12N, and -13N) were derived from surgically resected tissues taken out of patients with esophageal squamous cell carcinoma. Immortalized EC cells (EPC2-hTERT) cells, which remain diploidity and intact functions of p53 and Rb pathways (Harada H. et al, Mol. Cancer Res. 2004), were a generous gift from Drs. A.K. Rustgi and H. Nakagawa (Univ. of Penn.). Five (5) sophageal cancer cell lines (TE-1, -4, -5, -8, and -10) were also used in this study. Adenoviral transduction of REIC/Dkk-3 was done to determine antiproliferative effect in cancer cells. Resected esophageal cancer tissues were used for immunohistochemical staining. Western blot was performed to assess protein expressions. Flowcytometry was carried for cell cycle analysis.    [Results] Protein expression of REIC/Dkk-3 was detected in normal EE cells while none of 5 cancer cell lines determined had a detectable level of the protein. Immunohistochemistry using clinical tissues revealed a certain tendency of decreased expression of REIC/Dkk-3 in cancerous area. Interestingly, there is no/faint expression of REIC/Dkk-3 observed in normal esophageal keratinocytes on the basal layer of normal esophageal mucosa, where the cells are recognized the most proliferative, and expression was higher above suprabasal layers, suggesting that REIC/Dkk-3 expression may be involved in proliferative status of esophageal cells. When REIC/Dkk-3 gene was adenovirally transduced, Cell proliferation was suppressed with accumulation of cell population at G1 phase in TE-4 cells, while it did not affect cell growth of EPC2-hTERT cells. Western blot revealed decrease of cyclinD1 expression in the cancer cells but not in EPC2-hTERT cells.[Conclusion] REIC/Dkk-3 expression is likely related with cell proliferation and its forced expression leads to cancer-specific cell cycle arrest. REIC/Dkk-3 should be expected as a novel therapeutic gene for esophageal cancer.
Abstract P170: The Association of Serum Potassium with Mortality in Older Community-Dwelling Individuals: The Cardiovascular Health Study (CHS)
Authors: Jan M Hughes-Austin, Dena E Rifkin, Ronit Katz, Mark J Sarnak, Rajat Deo, David S Siscovick, Nona Sotoodehnia, Bruce M Psaty, Ian H De Boer, Bryan R Kestenbaum, Michael G Shlipak, Joachim H Ix
Journal: Circulation (2015)

Background: High serum potassium (K) is associated with death in chronic kidney disease (CKD) patients, and in acute illness. Associations in other settings are uncertain. We determined associations between K concentrations and total mortality, coronary heart disease (CHD) death, and sudden cardiac death (SCD) in an older, community-dwelling population. Methods: Among 5137 CHS participants aged ≥ 65 years at baseline, we evaluated associations between serum K categories [&lt; 4.0, 4.0-4.5, 4.5-5.0, &amp; ≥ 5.0 mMol/dL] with CHD death, SCD, and all-cause mortality using Cox proportional hazards models. We also evaluated whether associations differed by angiotensin converting enzyme (ACE) inhibitor / angiotensin II receptor blocker (ARB) use, diuretic use, and CKD status [eGFR &lt; 60 vs. higher]. All CHD and SCD events were adjudicated by committee. Results: Mean age was 72 years, 39% were male, and 17% were Black. Individuals in the ≥ 5.0 mMol/dL category were older, more frequently men, diabetic, to have CKD, and to use ACE/ARBs. They were also less likely to use diuretics. Mean follow-up was 14 ± 6 years during which there were 4122 total deaths including 971 CHD deaths. Follow-up for SCD was 12 ± 5 years during which there were 162 SCD events. In models adjusted for demographics, CVD risk factors, eGFR, and use of ACE/ARBs, diuretics and K supplements, those with K ≥ 5.0 mMol/dL had 32% higher risk of all-cause mortality (HR 1.32; 95% CI: 1.07-1.63) than the 4.0-4.5mMol/dL reference category. The association was similar irrespective of diuretic or ACE/ARB use or by CKD status (p interaction all &gt; 0.18). Those with K &lt; 4.0 mMol/dL had 14% higher risk of all-cause mortality (HR 1.14; 95% CI: 1.05-1.23) than the reference category; and this association was limited to those with K &lt; 4.0 mMol/dL and were not on diuretics and did not have CKD (p interaction both &lt; 0.02). No association of K &lt; 4.0 mMol/dL with mortality was observed in those on diuretics or with CKD. There was no significant association of either high or low K with either CHD death (HR 1.08; 95% CI: 0.71-1.65; and HR 0.96; 95% CI: 0.81-1.13, respectively) or SCD (HR 1.13; 95% CI: 0.41-3.11; and HR 1.01; 95% CI: 0.68-1.50, respectively) in adjusted models. Conclusions: Higher and lower serum K are independently associated with all-cause mortality but not CHD death or SCD in older community-dwelling individuals. Mechanisms linking high and low K with mortality from diseases other than CHD and SCD require future study.
Abstract 16852: Inhibition of Hypoxia-Inducible Factor Prolyl Hydroxylase Reduces Infarct Size and Improves Cardiac Function in a Rat Model of Myocardial Ischemia Reperfusion Injury
Authors: Pierre Signore, Zhihua Wei, Cyra Fung, Loren Russell, Michael Arend, Lee Flippin, Gail Walkinshaw, Ughetta del Balzo
Journal: Circulation (2011)

Hypoxia-inducible factor (HIF) has been shown to have cardioprotective effects when stabilized prior to a cardiac ischemic event. In the present studies, we investigated the cardioprotective effects of HIF stabilization post-ischemia, at the time of reperfusion, using the HIF prolyl-hydroxylase inhibitor (HIF-PHI) FG-6515. In a first study, the left coronary artery was temporarily ligated in rats to induce myocardial infarction (MI). After 30 minutes of ischemia, the ligature was removed, the myocardium was reperfused and FG-6515 (2, 6 or 20 mg/kg) or vehicle was administered once intravenously. Twenty-four hours after reperfusion, heart sections were stained with triphenyl tetrazolium chloride to measure infarct size as a percentage of the area at risk (AAR). FG-6515 given at reperfusion significantly decreased infarct size in a dose dependent manner (Table 1) and induced non-significant decreases in serum cardiac troponin I. In a second study using the same MI procedure, FG-6515 (20 mg/kg) was administered either once at reperfusion or 3 times (at reperfusion, 24 and 48 hours post-reperfusion). In addition, an MI group and a sham group received vehicle. Twenty-eight days after reperfusion, a Millar catheter was inserted in the left ventricle to measure cardiac function. FG-6515 significantly improved ejection fraction (EF), end-systolic volume (ESV) and relaxation time constant (RT). Three administrations of FG-6515 at daily intervals for the first 48 hours after reperfusion were more efficacious than a single administration (Table 2). In conclusion, these data support the use of HIF-PHI at reperfusion to limit infarct size and improve cardiac function after MI.
Abstract 16751: Life-Threatening Arrhythmias During Wearable Cardioverter Defibrillator Use
Authors: Nicole R Bianco, Jackie Sun, Steven J Szymkiewicz
Journal: Circulation (2014)

Background:  Recent emergency medicine studies have suggested that asystoles are increasing as the presenting arrhythmia of sudden cardiac arrest (SCA), with a proportional reduction in shockable ventricular arrhythmias (VT/VF). This is an important trend since successful resuscitation approaches are directly related to the presenting rhythm. The current wearable cardioverter defibrillator (WCD) is designed to record and alarm for both sustained VT/VF and asystole, providing a treatment shock for VT/VF and voice alerts to “Call for help. Perform CPR” for asystole. The objective of this study was to determine whether there has been a change in the proportion of VT/VF versus asystole as the initial presenting arrhythmia over the past 8 years of commercial WCD use.   Methods:  All asystole or treated VT/VF events that were recorded by the WCD (LifeVest®, ZOLL) from 2006-2013 were retrospectively analyzed. An event was defined as all arrhythmias occurring within a 24 hour period. Events were classified as asystole if the initial presenting rhythm was asystole (with at least a 5 second pause) and as VT/VF if the initial presenting rhythm was sustained VT/VF.   Results:  Over eight years, 2184 patients (pts) (74% male, age 64 ± 13 years) had 1686 treated VT/VF events and 702 asystole events. Pts who had an asystole event were older than those who had a VT/VF event (67 ± 11 versus 63 ± 13, respectively)(p   Conclusions:  The WCD provides a unique opportunity to record ECG rhythms at the onset of a potential SCA and prior to defibrillation. This study suggests that the majority of arrhythmias initially present as VT/VF, which is amenable to defibrillation therapy, and the rate of asystoles as the presenting rhythm has not significantly changed over the past eight years of WCD use.
Genetic Factors Predicting The Response To BET Bromodomain Inhibitors In Lymphoma Lead To New Synergistic Combinations
Authors: Eugenio Gaudio, Ivo Kwee, Andrea Rinaldi, Michela Boi, Elena Bernasconi, Monica Testoni, Anastasios Stathis, Patrice Herait, Kay Noel, Giorgio Inghirami, Emanuele Zucca, Francesco Bertoni
Journal: Blood (2013)
Fragile X–Associated Tremor/Ataxia Syndrome in a Man in His 30s
Authors: Verónica Martínez-Cerdeño, Mirna Lechpammer, Aisha Lott, Andrea Schneider, Randi Hagerman
Journal: JAMA Neurology (2015)

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s1,2 and affects carriers of premutation expansion (55–200 CGG repeats) of the fragile × mental retardation 1 (FMR1) gene. It is caused by elevated levels of FMR1 messenger RNA, leading to toxicity. Clinical features include progressive cerebellar ataxia and intention tremor. Associated symptoms include autonomic dysfunction, peripheral neuropathy, and cognitive impairment2.
An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology
Authors: Richard T. Silver, Steven H. Woolf, Rüdiger Hehlmann, Frederick R. Appelbaum, James Anderson, Charles Bennett, John M. Goldman, Francois Guilhot, Hagop M. Kantarjian, Alan E. Lichtin, Moshe Talpaz, Sante Tura
Journal: Blood (1999)
Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections
Authors: Gareth Morris-Stiff, Gabriele Marangoni, Abdul Hakeem, Shahid G. Farida, Dhanwant Gomez, Giles J. Toogood, J. Peter A. Lodge, K. Raj Prasad
Journal: International Journal of Surgery (2015)
Compound heterozygosity for hemoglobin C and Korle-Bu: moderate microcytic hemolytic anemia and acceleration of crystal formation [corrected] [published erratum appears in Blood 1994 May 15;83(10):3105]
Authors: RL Nagel, MJ Lin, HE Witkowska, ME Fabry, M Bestak, RE Hirsch
Journal: Blood (1993)
Abstract 8142: By Virtue of Its Interaction with the {beta}2-adrenergic Receptor, CXCR4 Plays a Role in the Regulation of {beta}2-adrenergic Receptor Signaling Pathway Affecting Calcium and Contractility in Cardiac Myocytes
Authors: Thomas LaRocca, Hunter Champion, Georges Haddad, Roger Hajjar, Lakshmi Devi, Alison Schecter, Sima T Tarzami
Journal: Circulation (2011)

Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation, metastasis, and embryonic development. We previously demonstrated a nonchemotactic role ...
Baseline Low-Density Lipoprotein Cholesterol Is an Important Predictor of the Benefit of Intensive Lipid-Lowering Therapy
Authors: Roberto R. Giraldez, Robert P. Giugliano, Satishkumar Mohanavelu, Sabina A. Murphy, Carolyn H. McCabe, Christopher P. Cannon, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2008)
Combined integrin siRNA therapy and radiotherapy of breast cancer.
Authors: Qizhen Cao, Tianfang Li, Weibo Cai, Xianzhong Zhang, Kai Chen, Yong Yang, Lei Xing, Xiaoyuan Chen
Journal: Cancer Research (2006)

5175   Objective: Radiation induces the expression of α v β 3  integrin, which is shown to play a key role in tumor angiogenesis and metastasis. We testified the effect of integrin α v β 3  in tumor resistance to irradiation and evaluated the anti-cancer efficacy of combining integrin α v  siRNA therapy with irradiation to treat breast cancer. Methods: Wild-type and α v  integrin siRNA (10 nM) transfected human breast cancer MDA-MB-435 cells were irradiated with different doses of X-rays, and the radiosensitivity of these cells were evaluated by clonogenic survival assay. To determine whether siRNA treatment against α v β 3  integrin could enhance the efficacy of irradiation, MDA-MB-435 cells were divided into 5 groups: control; non-specific siRNA; α v  integrin siRNA; irradiation; combination of siRNA and irradiation. The treatment effect was assessed by cell proliferation assay. Integrin expression levels and the influence of siRNA pre-treatment on cell cycle were measured by flow cytometry. Results: Survival curve showed that MDA-MB-435 cells pre-treated with siRNA (low α v β 3  integrin expression) are more responsive to irradiation than wild-type cells (high α v β 3  integrin expression). The anti-tumor effect of combination therapy is much better than either siRNA or irradiation treatment alone. Flow cytometry showed thatα v β 3  integrin expression increased in the irradiation group while the α v β 3  expression in siRNA or combination group decreased. Furthermore, cell cycle analysis showed that transfection with α v  integrin siRNA increased G 2 -M arrest of irradiated cells. Conclusion: Gene silencing with α v  integrin siRNA can increase the radiosensitivity of MDA-MB-435 cells. The combination of siRNA treatment and irradiation is more effective than either treatment modality alone.
Abstract 1594: Increased Apoptosis in Compensated Pressure Overload is not Related to the Extent of Hypertrophy and Occurs in Interstitial Non-Myocytes
Authors: Ricardo Gelpi, You-Tang Shen, Dorothy E Vatner, Stephen F Vatner
Journal: Circulation (2008)

A number of studies have indicated a direct relationship between the degree of apoptosis and the severity of left ventricular (LV) hypertrophy (H). However, most of these studies have been carried out in animal models in which pressure overload causes myocardial fiber stretching, as assessed by LV dilation and an increase in LV end diastolic pressure (EDP). In addition, these studies did not discern whether the apoptosis occurred in myocytes or other cell types in the cardiac interstitium. To study the frequency of apoptosis associated with LVH in the absence of fiber stretching, we studied a canine model in which pressure overload, from chronic aortic stenosis, results in a model of concentric LVH, with doubling of LV/body weight, but where the LV is not dilated and LV systolic function, as assessed by LV dP/dt max, (3433±188 mmHg/sec) and LV end diastolic pressure (12±2 mmHg) is normal. The TUNEL method was used to assess changes in apoptosis in cardiac myocytes and interstitial cells in the presence of LVH. Myocyte cross-sectional area was calculated histologically. In control dogs (n=4), the rate of apoptosis in myocytes was 0.03±0.01%. The rate of apoptosis in dogs with LVH (n=6) did not increase significantly, and there was a negative correlation (r= −0.51) between the extent of LVH and the increased apoptotic rate, which was also non-significant. In marked contrast, the rate of apoptosis of non-myocytes (interstitial cells) rose from normal values of 0.03±0.01% to 0.13±0.03%, p 2 ) than in the endocardium (396±4 micron 2 ) of LVH dogs, but the apoptotic rate was similar in both endo and epicardium, demonstrating further a lack of association between LVH and myocyte apoptosis. Thus, myocyte apoptosis does not increase in response to pressure overload LVH in the absence of LV dilation and elevated LVEDP, suggesting that it is the LV dilation and stretching of myocardium, superimposed on LVH, which may be responsible for the prior reports of increased apoptosis.