tbuckley/cabot-search huggingface dataset:
Evaluation of an auto-nCPAP device based on snoring detection
Authors: F Lofaso, AM Lorino, D Duizabo, H Najafi Zadeh, D Theret, F Goldenberg, A Harf
Journal: European Respiratory Journal (1996)

We evaluated an auto-nasal continuous positive airway pressure (nCPAP) prototype (MC+; SEFAM, Nancy, France) in which apnoea/hypopnoea detection was disabled and nasal mask pressure vibration detection was the only mode of pressure setting. The device was tested in 15 previously untreated obstructive sleep apnoea patients during a night with polysomnography. We observed that a single night of auto-nCPAP improved the apnoea/hypnoea index (AHI) (12 +/- 21 vs 51 +/- 31 disordered breathing events.h-1 of sleep (mean +/- SD)), the awakening-arousal index (13 +/- 20 vs 40 +/- 26 arousals.h-1 of sleep), and duration of slow wave sleep (102 +/- 49 vs 71 +/- 56 min) but not of rapid eye movement (REM) sleep (55 +/- 31 vs 64 +/- 38 min). Auto-nCPAP was effective (apnoea/hypopnoea and arousal indices < 10 events.h-1) in all but three patients. Auto-nCPAP was ineffective in one patient, whose obstructive respiratory events were not preceded by nasal mask pressure vibration detection, and in two patients who were quasi-permanent mouth breathers. Snoring detection may be effective in sleep apnoea syndrome with heavy snoring and without permanent mouth breathing, during the first night of nasal continuous positive airway pressure treatment.
Effects of Terbutaline and Budesonide on Sputum Cells and Bronchial Hyperresponsiveness In Asthma
Authors: RUTH E. ALDRIDGE, ROBERT J. HANCOX, D. ROBIN TAYLOR, JAN O. COWAN, MARTI C. WINN, CHRIS M. FRAMPTON, G. IAN TOWN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Previous studies have shown that the regular administration of short acting β -agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proinflammatory mechanism. The aim was to explore possible adverse effects of high-dose β -agonist therapy and to assess any adverse interaction with corticosteroids. We undertook a randomized, crossover study to investigate the effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 μ g twice a day), combined treatment, and placebo in subjects with mild to moderate asthma. Major endpoints were PD15 saline, PD20 methacholine, and induced sputum differential cell counts. Thirty-four subjects were randomized and 28 completed the study. PD15 saline decreased on terbutaline alone compared with placebo treatment and on combined treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% CI = 0.43, 0.97], respectively). PD20 methacholine was not affected by the use of terbutaline either alone or in combination with budesonide. The percentage of eosinophils in induced sputum increased during terbutaline treatment alone compared with placebo (median 8.3% versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did not affect the percentage of eosinophils compared with budesonide treatment alone. These findings support the hypothesis that short-acting β -agonists have a permissive effect on airway inflammation and that when used in high dose there may be an unfavorable interaction with inhaled corticosteroids.
Randomized Multicenter Phase II Trial of Bolus Plus Infusional Fluorouracil/Leucovorin Compared With Fluorouracil/Leucovorin Plus Oxaliplatin As Third-Line Treatment of Patients With Advanced Colorectal Cancer
Authors: Nancy Kemeny, Carlos A. Garay, Jayne Gurtler, Howard Hochster, Peter Kennedy, Al Benson, Debra Schwab Brandt, Jonathan Polikoff, Michael Wertheim, Grace Shumaker, Doreen Hallman, Brent Burger, Sunil Gupta
Journal: Journal of Clinical Oncology (2004)

The addition of oxaliplatin to fluorouracil (FU) and leucovorin (LV) improves the outcome of patients with colorectal cancer (CRC). This multicenter study evaluated FU/LV with or without oxaliplatin in patients with metastatic CRC after disease progression on sequential fluoropyrimidine and irinotecan.Two hundred fourteen patients were randomly assigned to receive LV 200 mg/m2 intravenously (IV) and FU 400 mg/m2 IV bolus, followed by FU 600 mg/m2 IV over 22 hours on days 1 and 2, every 2 weeks (LV5FU2); or LV and FU as described, plus oxaliplatin 85 mg/m2 IV over 2 hours on day 1 of the schedule (FOLFOX4). The primary end point was overall response.Baseline characteristics were similar in the two treatment arms. Objective response (complete + partial) rates for LV5FU2 versus FOLFOX4 were 2% v 13% (P = .0027), respectively. Median time to disease progression was 2.4 v 4.8 months (P < .0001), and median survival was 11.4 v 9.9 months (P = .20) for LV5FU2 and FOLFOX4, respectively. Among the 72 patients who crossed over from LV5FU2 to FOLFOX4, 6% responded. Symptomatic improvement was significantly better for patients in the FOLFOX4 arm (32% v 18% for LV5FU2, P = .05). Grade 3/4 toxicities for LV5FU2 and FOLFOX4 were neutropenia (13% and 42%, respectively), diarrhea (6% and 16%, respectively), and overall neuropathy (0% and 6%, respectively).In patients with metastatic CRC, the FOLFOX4 regimen was superior to LV5FU2 with a higher response rate and time to disease progression. FOLFOX4 is an effective regimen even after disease progression on two previous chemotherapy regimens with fluoropyrimidines and irinotecan.
Does Helicobacter pylori protect against asthma and allergy
Authors: M Wjst
Journal: Gut (2008)

We read with interest the article by Zullo et al ( Gut 2007; 56 :1353) on the sequential therapy regimen for Helicobacter pylori eradication that supports the conclusion that this regimen achieves higher eradication rates than standard triple therapies. In the article, paediatric experience with this new therapy is reported based on two trials by our group which reported an overall eradication rate of 88.5%.

H pylori infection plays a crucial role in the pathogenesis of both chronic active gastritis and peptic ulcer disease in children, and it is considered as an essential risk factor for the development of gastric carcinoma; moreover, younger age at acquisition has been suggested to increase the risk of developing cancer later …
A novel autoantibody test for the detection of pre-neoplastic lung lesions
Authors: Frazer J Lowe, Weike Shen, Jinchi Zu, Junfu Li, Hao Wang, Xufei Zhang, Li Zhong
Journal: Molecular Cancer (2014)

Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. Detection of AAH and SCD has been achieved by imaging and bronchoscopy clinically, but sensitivity and specificity remain less than satisfactory. We utilized the ability of the immune system to identify lesion specific proteins for detection of AAH and SCD.AAH and SCD tissue was surgically removed from six patients of Chinese descent (3 AAH and 3 SCD) with corresponding serum samples. Total RNA was extracted from the tissues and a cDNA library was generated and incorporated into a T7 bacteriophage vector. Following enrichment to remove "normal" reactive phages, a total of 200 AAH related and 200 SCD related phage clones were chosen for statistical classifier development and incorporation into a microarray. Microarray slides were tested with an independent double-blinded population consisting of 100 AAH subjects, 100 SCD subjects and 200 healthy control subjects.Sensitivity of 82% and specificity of 70% were achieved in the detection of AAH using a combination of 9 autoantibody biomarkers. Likewise, 86% sensitivity and 78% specificity were achieved in the detection of SCD using a combination of 13 SCD-associated markers. Sequencing analysis identified that most of these 22 autoantibody biomarkers had known malignant associations.Both diagnostic values showed promising sensitivity and specificity in detection of pre-neoplastic lung lesions. Hence, this technology could be a useful non-invasive tool to assess lung cancer risk in human populations.
Allogeneic Hematopoietic Cell Transplantation for Metastatic Renal Cell Carcinoma after Nonmyeloablative Conditioning
Authors: Scott S. Tykodi, Edus H. Warren, John A. Thompson, Stanley R. Riddell, Richard W. Childs, Brith E. Otterud, Mark F. Leppert, Rainer Storb, Brenda M. Sandmaier
Journal: Clinical Cancer Research (2004)

Abstract Purpose: This phase I trial assessed the safety, efficacy, and immunologic responses to minor histocompatibility antigens following nonmyeloablative allogeneic hematopoietic cell transplantation as treatment for metastatic renal cell carcinoma. Experimental Design: Eight patients received conditioning with fludarabine and low-dose total body irradiation followed by hematopoietic cell transplantation from an HLA-matched sibling donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for donor engraftment of myeloid and lymphoid cells, for clinical response by serial imaging, and for immunologic response by in vitro isolation of donor-derived CD8+ CTLs recognizing recipient minor histocompatibility (H) antigens. Results: All patients achieved initial mixed hematopoietic chimerism with two patients rejecting their graft and recovering host hematopoiesis. Four patients developed acute, grade 2 to 3, graft-versus-host disease and four patients developed extensive chronic graft-versus-host disease. Five patients had progressive disease, two patients had stable disease, and one patient experienced a partial response after receiving donor lymphocyte infusions and IFN-α. CD8+ CTL clones recognizing minor H antigens were isolated from five patients studied. Clones from three patients with a partial response or stable disease recognized antigens expressed on renal cell carcinoma tumor cells. Conclusions: Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. CD8+ CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft-versus-tumor effect. Such antigens may represent therapeutic targets for posttransplant vaccination or adoptive T-cell therapy to augment the antitumor effects of allogeneic hematopoietic cell transplantation.
Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity
Authors: Guido Lammering, Theodore H. Hewit, Mathew Holmes, Kristoffer Valerie, William Hawkins, Peck-Sun Lin, Ross B. Mikkelsen, Rupert K. Schmidt-Ullrich
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The commonly expressed variant epidermal growth factor receptor (EGFR), the type III EGFR variant (EGFRvIII), functions as an oncoprotein promoting neoplastic transformation and tumorigenicity. The role of EGFRvIII in cellular responses to genotoxic stress, such as ionizing radiation, is only minimally defined. Thus, we have investigated EGFRvIII as a potential modulator of cellular radiation responses and explored the feasibility of adenovirus (Ad)-mediated expression of dominant-negative EGFR-CD533 as a gene therapeutic approach for inhibiting EGFRvIII function in vitro and in vivo. Experimental Design and Results: EGFR-CD533 and EGFRvIII were expressed in vitro and in vivo in malignant U-373 MG glioma cells through transduction with an Ad vector, Ad-EGFR-CD533 and Ad-EGFRvIII, respectively. In vivo studies defined the importance of EGFRvIII as a modulator of radiation responses, demonstrating a 2.6-fold activation of EGFRvIII in U-373 malignant glioma tumors. Concomitant expression of EGFR-CD533 inhibited the radiation-induced activation of EGFRvIII in vitro and completely abolished the enhanced clonogenic survival conferred by EGFRvIII. The ability of EGFR-CD533 to inhibit EGFRvIII function was further confirmed in vivo through complete inhibition of EGFRvIII-mediated increased tumorigenicity and radiation-induced activation of EGFRvIII. Growth delay assays with U-373 xenograft tumors demonstrated that the expression of EGFR-CD533 significantly enhanced radiosensitivity of tumor cells under conditions of intrinsic and Ad-mediated EGFRvIII expression. Conclusions: We conclude that EGFRvIII confers significant radioresistance to tumor cells through enhanced cytoprotective responses, and we have demonstrated that dominant-negative EGFR-CD533 effectively inhibits EGFRvIII function. These data affirm the broad potential of EGFR-CD533 to radiosensitize human malignant glioma cells.
Proper inhaler's technique closely related to proper instruction
Authors: Maggie Lit Pik Kee, Kuen Han Lee, Amy Tsoi Lai Fong
Journal: European Respiratory Journal (2012)

Introduction:   Evidence suggests that many patients don9t use their meter dose inhalers (MDI) correctly and mostly related to improper instruction.   Objectives   It is an observational pre & post-lecture assessment study aims to assess the knowledge and practical competency of the nurses.   Methodology   The assessment items including 4 categories, applicable to only MDI and Spacer inhaler device:  1  patient observation  2  drug explanation to patients  3  choice of assisting device  4  instruction on how to use inhalers or spacer  5  monitoring the effect & side effect and reporting.  Four identical sessions of 1.5-hour lectures including hands-on workshops on inhalers have been held from September to October 2011. Returned demonstration and compulsory audit assessment were required pre and post lectures with 2 months intervals.   Results   54 nurses completed the pre-lecture audit and 87 % were registered nurses. 30% had at least 5 years9 medical experience but none show full competence in demonstrating all 14 steps for MDI and 12 steps for spacer correctly. The mean steps of MDI & spacer are only 5.6 and 6.6 respectively. A total of 32 nurses had attended the lectures and amongst which 26 nurses had performed the pre-and post-audit assessment. A significant improvement is found in mean steps for MDI (4.4 vs. 10.3) and spacer (5.7 vs. 10.25) The overall post-audit mean steps are 10.09 for MDI and 10.43 for spacer respectively (p   Conclusion   Proper inhaler technique depends on proper instructions. MDI and spacers checklists have been formulated and revised for providing step by step guidance. A regular training workshops and lectures will be held quarterly.
DNA Damage–Dependent Translocation of B23 and p19ARF Is Regulated by the Jun N-Terminal Kinase Pathway
Authors: Orli Yogev, Keren Saadon, Shira Anzi, Kazushi Inoue, Eitan Shaulian
Journal: Cancer Research (2008)

The dynamic behavior of the nucleolus plays a role in the detection of and response to DNA damage of cells. Two nucleolar proteins, p14(ARF)/p19(ARF) and B23, were shown to translocate out of the nucleolus after exposure of cells to DNA-damaging agents. This translocation affects multiple cellular functions, such as DNA repair, proliferation, and survival. In this study, we identify a pathway and scrutinize the mechanisms leading to the translocation of these proteins after exposure of cells to DNA-damaging agents. We show that redistribution of B23 and p19(ARF) after the exposure to genotoxic stress occurs preferentially when the c-Jun-NH(2)-kinase (JNK) pathway is activated and is inhibited when the JNK pathway is impaired. The stress-induced translocation of alternative reading frame (ARF) is JNK dependent and mediated by two activator proteins, c-Jun and JunB. Thr(91) and Thr(93) of c-Jun are required for the translocation, but the transcriptional activity of c-Jun is dispensable. Instead, c-Jun interacts with B23 in a dose-dependent manner. c-Jun itself is excluded from the nucleolus in a JNK-dependent manner. Hence, we suggest that c-Jun translocates B23 and ARF from the nucleolus after JNK activation by means of protein interactions. In senescent cells, JNK activity and c-Jun levels are reduced concomitantly with ARF nucleolar accumulation, and UV radiation does not cause the translocation of ARF.
Bayesian Estimation of Nonsynonymous/Synonymous Rate Ratios for Pairwise Sequence Comparisons
Authors: K. Angelis, M. dos Reis, Z. Yang
Journal: Molecular Biology and Evolution (2014)

The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important measure of the mode and strength of natural selection acting on nonsynonymous mutations in protein-coding genes. The simplest such analysis is the estimation of the dN/dS ratio using two sequences. Both heuristic counting methods and the maximum-likelihood (ML) method based on a codon substitution model are widely used for such analysis. However, these methods do not have nice statistical properties, as the estimates can be zero or infinity in some data sets, so that their means and variances are infinite. In large genome-scale comparisons, such extreme estimates (either 0 or ∞) of ω and sequence distance (t) are common. Here, we implement a Bayesian method to estimate ω and t in pairwise sequence comparisons. Using a combination of computer simulation and real data analysis, we show that the Bayesian estimates have better statistical properties than the ML estimates, because the prior on ω and t shrinks the posterior of those parameters away from extreme values. We also calculate the posterior probability for ω > 1 as a Bayesian alternative to the likelihood ratio test. The new method is computationally efficient and may be useful for genome-scale comparisons of protein-coding gene sequences.
The PTEN pathway in Tregs functions as a critical driver of the immunosuppressive tumor microenvironment and tolerance to apoptotic cells
Authors: Madhav Sharma, Rahul Shinde, Tracy McGaha, Lei Huang, Rikke Holmgaard, Jedd Wolchok, Mario Mautino, Esteban Celis, Arlene Sharpe, Loise Francisco, Jonathan Powell, Hideo Yagita, Andrew Mellor, Bruce Blazar, David Munn
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The tumor microenvironment is profoundly immunosuppressive, but exactly how this is coordinated and maintained remains poorly understood. We show that multiple transplantable and autochthonous mouse tumors actively elicit a population of highly suppressive regulatory T cells (
Hospitals that follow heart attack guidelines save lives
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

More patients who have had a heart attack walk out the door alive when hospitals stick to guidelines of the American Heart Association and the American College of Cardiology, says a study from Duke University presented at the college's meeting in New Orleans, Louisiana.

It is one of the first studies to show the effect of guidelines on inhospital mortality in “real world patients,” said Dr Eric Peterson, a cardiologist at Duke Clinical Research Institute in Durham, North Carolina. “Typically, patients in randomised controlled trials are healthier and younger, good for testing efficacy of a drug. This population was older, sicker, at higher risk. …
Urokinase-Type Plasminogen Activator and Its Receptor in Bladder Cancer
Authors: Y. Hasui, Y. Osada
Journal: JNCI Journal of the National Cancer Institute (1997)

Two-locus linkage analysis of cutaneous malignant melanoma/dysplastic nevi. Am J Hum Genet 1996;58:1050-6. (30) Walker GJ, Nancarrow DJ, Walters MK, Palmer JM, Weber JL, Hayward NK. Linkage analysis in familial melanoma kindreds to markers on chromosome 6p. Int J Cancer 1994;59:771-5. (31) Frants RR, Van der Velden PA, Bergman W, Gruis NA. Melanocytestimulating hormone receptor (MC1R) variants modify melanoma risk in Dutch FAMMM families. Am J Hum Genet 1996;59 Suppl:A67. (32) MacKie R, Hunter JA, Aitchison TC, Hole D, Mclaren K, Rankin R, et al. Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group. Lancet 1992;339:971-5. (33) NIH Consensus Statement: diagnosis and treatment of early melanoma. NIH Consensus Development Conference, January 27-29, 1992, Vol. 10, No. 1.
Plasma and hepatic carnitine and coenzyme A pools in a patient with fatal, valproate induced hepatotoxicity.
Authors: S Krahenbuhl, G Mang, H Kupferschmidt, P J Meier, M Krause
Journal: Gut (1995)

Reduced hepatic mitochondrial beta-oxidation and changes in the plasma carnitine pool are important biochemical findings in valproate induced liver toxicity. The carnitine pools in plasma and liver and the liver coenzyme A (CoA) pool in a patient with fatal, valproate induced hepatotoxicity were measured. In plasma and liver the free and total carnitine contents were decreased, whereas the ratios short chain acylcarnitine/total acid soluble carnitine were increased. The long chain acylcarnitine content was unchanged in plasma, and increased in liver. The total CoA content in liver was decreased by 84%. This was due to reduced concentrations of CoASH, acetyl-CoA, and long chain acyl-CoA whereas the concentrations of succinyl-CoA and propionyl-CoA were both increased. The good agreement between the plasma and liver carnitine pools reflects the close relation between these two pools. The observed decrease in the hepatic CoASH and total CoA content has so far not been reported in humans with valproate induced hepatotoxicity and may be functionally significant.
Finite element analysis of myocardial diastolic function using three-dimensional echocardiographic reconstructions: application of a new method for study of acute ischemia in dogs.
Authors: D D McPherson, D J Skorton, S Kodiyalam, L Petree, M P Noel, R Kieso, R E Kerber, S M Collins, K B Chandran
Journal: Circulation Research (1987)

The effect of acute myocardial ischemia on the myocardial elastic modulus has been a matter of controversy. To evaluate this question, diastolic elastic modulus was assessed by finite element analysis of left ventricular geometry using three-dimensional echocardiographic reconstructions and right and left ventricular pressure recordings. Elastic properties were estimated before and after coronary occlusion in 6 open-chest dogs. Elastic modulus values were derived by means of a computer program that determined the global elastic modulus that best predicted the diastolic changes in left ventricular geometry. In the finite element analysis after coronary occlusion, two analyses were performed: one utilizing the control elastic modulus for all segments of the left ventricle and one in which ischemic (dyskinetic) segments were assigned a higher elastic modulus. Results showed that the control elastic modulus was a poor predictor of diastolic left ventricular expansion after coronary occlusion. The finite element analysis in which the ischemic segments were assigned a higher elastic modulus better predicted ischemic diastolic wall motion patterns. Error values (difference between predicted and actual left ventricular segmental diastolic motion) were: control, 1.9 +/- 0.3 mm (mean +/- SD), ischemia, 2.9 +/- 0.5 mm, and 2.2 +/- 0.4 mm using the stiffer elastic modulus for ischemic segments. Error values were significantly higher (p less than 0.05) under ischemic conditions when the control elastic modulus was uniformly applied compared with control and ischemia with dyskinetic segments assigned a higher elastic modulus. From these data, it is concluded that the myocardial diastolic elastic modulus is increased by ischemia and that this approach may allow clinical assessment of intrinsic muscle stiffness.