tbuckley/cabot-search huggingface dataset:
New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic
Authors: Erminia Massarelli, Renata Ferrarotto, Bonnie S. Glisson
Journal: Clinical Cancer Research (2015)

Abstract The past two decades have been witness to a steadily increasing incidence of oropharynx cancer, specifically related to human papillomavirus (HPV), primarily affecting middle-aged Caucasian men, in North America and Europe. The ever-increasing incidence, now clearly an epidemic, of this unique clinicopathologic entity demands new perspectives in diagnosis and staging and presents unique challenges in clinical research, given the excellent prognosis afforded by chemoradiation for the majority of these patients. To reduce the morbidity of late toxicity in survivors without compromising the high rates of survival currently enjoyed, and simultaneously address the poor prognosis of those with recurrence, it is critical to capitalize on the viral etiology and translate discoveries in genomics, target/drug discovery, viral oncogenesis, and immunbiology to improved outcomes for patients. Herein, we review ongoing and planned clinical research for HPV-related oropharynx cancer, the basis for which is constituted by prior clinical observations, knowledge of the genomic alterations and altered biology associated with HPV-related oncogenesis, and hope that molecularly targeted and immunomodulatory therapies can be harnessed. Clin Cancer Res; 21(17); 3821–8. ©2015 AACR.
Responsiveness of the six-minute stepper test to pulmonary rehabilitation in patients with COPD
Authors: Romain Pichon, Marc Beaumont, Catherine Le Ber-Moy, Chantal Lochon, Loic Peran, Francis Couturaud
Journal: European Respiratory Journal (2014)

Background:  The six-minute stepper test (6MST) validity and reproducibility have already been demonstrated in patients with chronic obstructive pulmonary disease (COPD).   Aims:  To evaluate the responsiveness of the 6MST to pulmonary rehabilitation (PR) in patients with COPD and to objectively compare 6MST and six-minute walk test (6MWT).   Methods:  62 patients with COPD were included in this prospective cohort study. Participants underwent a three weeks inpatient PR program. Two 6MST and two 6MWT were performed before PR and one 6MST and one 6MWT were performed after the program. The primary outcome was the evolution of the number of steps during the 6MST before and after PR. Secondary outcome included the evolution of the six-minute walk distance (6MWD) pulse oxymetry, heart rate, dyspnea and leg discomfort during the tests before and after PR.   Results:  A significant increase in the number of steps during the 6MST was observed after PR (22.5 steps; 95% CI: 13.8-31.3; pl0.0001) and in the 6MWD after PR (26.6 m; 95% CI: 17.6-35.5; pl0.0001). 6MST and 6MWT improved by 10.1% and 6.5%, respectively. The number of steps during the 6MST was significantly correlated with the 6MWD before (r=0.72; pl0.0001) and after PR (r=0.66; pl0.0001).   Conclusion:  The 6MST appears to be as responsive as the 6MWT in order to assess functional improvement during PR in patients with COPD. The 6MST is low cost and requires limited space.
Paclitaxel Resistance in Non–Small-Cell Lung Cancer Associated With Beta-Tubulin Gene Mutations
Authors: Mariano Monzó, Rafael Rosell, José Javier Sánchez, Jin S. Lee, Aurora O'Brate, José Luis González-Larriba, Vicente Alberola, Juan Carlos Lorenzo, Laura Núñez, Jae Y. Ro, Cristina Martín
Journal: Journal of Clinical Oncology (1999)

The mechanisms that cause chemoresistance in non-small-cell lung cancer (NSCLC) patients have yet to be clearly elucidated. Paclitaxel is a tubulin-disrupting agent that binds preferentially to beta-tubulin. Tubulins are guanosine triphosphate (GTP)-binding proteins. Beta-tubulin is a GTPase, whereas alpha-tubulin has no enzyme activity. We reasoned that polymerase chain reaction (PCR) and DNA sequencing of the beta-tubulin gene could reveal more information regarding the connection between beta-tubulin mutations and primary paclitaxel resistance.Constitutional genomic DNA and paired tumor DNA were isolated from 49 biopsies from 43 Spanish and six American stage IIIB and IV NSCLC patients who had been treated with a 3-hour, 210 mg/m(2) paclitaxel infusion and a 24-hour, 200 mg/m(2) infusion, respectively. Oligonucleotides specific to beta-tubulin were designed for PCR amplification and sequencing of GTP- and paclitaxel-binding beta-tubulin domains.Of 49 patients with NSCLC, 16 (33%; 95% confidence interval [CI], 20.7% to 45.3%) had beta-tubulin mutations in exons 1 (one patient) or 4 (15 patients). None of the patients with beta-tubulin mutations had an objective response, whereas 13 of 33 (39.4%; 95% CI, 22.8% to 56%; P = 0.01) patients without beta-tubulin mutations had complete or partial responses. Median survival was 3 months for the 16 patients with beta-tubulin mutations and 10 months for the 33 patients without beta-tubulin mutations (P =.0001).We have identified beta-tubulin gene mutations as a strong predictor of response to the antitubulin drug paclitaxel; these mutations may represent a novel mechanism of resistance and should be examined prospectively in future trials of taxane-based therapy in NSCLC.
Asherman's syndrome: A review of the literature, and a husband and wife's 20-year world-wide experience
Authors: Kenneth Chapman, Roxana Chapman
Journal: Journal of the Royal Society of Medicine (1990)

Asherman's syndrome is reviewed, and 27 cases treated by us in Iran, England, New Zealand and Australia over a 20-year period are analysed. Aetiological factors and treatment are discussed. In view of the high incidence of complications in subsequent pregnancies, the need for prevention is stressed. Although more common in some countries, it is, nevertheless, of world-wide distribution and, unless looked for, will be missed.
Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease
Authors: Ankur Pandya, Stephen Sy, Sylvia Cho, Milton C. Weinstein, Thomas A. Gaziano
Journal: JAMA (2015)

The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins.To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines.Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources.Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained.In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY.In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (≥7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0% risk threshold) or $150,000/QALY (≥3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.
Multidisciplinary Evaluation of Diabetic Impotence
Authors: Kemal Sarica, Nihat Arikan, Ahmet Serel, Zehra Arikan, Suat Aytaç, Adil Çulcuoğlu, Fahri Bayram, L. Sezai Yaman, Sadettin Küpeli
Journal: European Urology (1994)
LSC 2011 Abstract: Thymic stromal lymphopoietin is a central regulator of anti-viral CD8+ T cell response
Authors: Koshika Yadava, Sichelstiel Anke, Aurelien Trompette, Nicola Harris, Benjamin Marsland
Journal: European Respiratory Journal (2011)

TSLP is an IL-7 like cytokine that is primarily produced by epithelial cells at mucosal surfaces. It has been widely studied in Th2-driven inflammatory disorders such as atopic dermatitis and asthma. Although both viral nucleic acid analogues and pro-inflammatory cytokines associated with active viral infections are potent stimulators of TSLP expression in vitro, it9s role in antiviral immunity is unknown. To elucidate the role of TSLP in viral infections, we investigated the immune response against influenza A in mice deficient in TSLPR. We found that TSLPR-deficient mice exhibited impaired clearance of the virus at late time points post infection, indicative of a defect in the adaptive immune response. Although priming in the lymph node was unaffected, the virus-specific CD8+ T cell response in the lung was compromised in the absence of TSLPR. This defect was characterized by the reduced frequency of virus-specific CD8 T cells as well as reduced effector functions such as granzyme B expression and interferon-γ production. Using mixed bone marrow chimeras and adoptive transfer studies, our data suggests that TSLP affects influenza-specific responses by modulating the function of recruited inflammatory dendritic cells (DCs). Pulmonary DCs isolated from infected lungs of TSLPR deficient mice were defective in inducing proliferation of antigen specific naive T cells in vitro. Furthermore in the absence of TSLPR the production and trans presentation of IL-15 by CD11b+ inflammatory DC was impaired. We propose that TSLP regulates activation of antigen specific cytotoxic T cells at the site of infection by modulation of DC function and suggest a crucial link between TSLP and IL-15 production during infection.
Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy
Authors: Nicola Fossati, R. Jeffrey Karnes, Cesare Cozzarini, Claudio Fiorino, Giorgio Gandaglia, Steven Joniau, Stephen A. Boorjian, Gregor Goldner, Wolfgang Hinkelbein, Karin Haustermans, Bertrand Tombal, Shahrokh Shariat, Pierre I. Karakiewicz, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel, Alberto Briganti
Journal: European Urology (2015)
Nasal pressure variation measurement with a microphone: A new low cost tool for diagnosis of obstructive sleep apnoea in a resource poor setting
Authors: Chatura Wirasinghe, Srini Godevithanage, Dushantha Madegedara
Journal: European Respiratory Journal (2012)

Background   Lack of polysomnography in Sri Lanka leads to under investigation of OSA. Nocturnal saturation (SPO 2 ) was used instead. Pressure variations due to turbulent flow through nose measured by a microphone fixed to a nasal cannula can be demonstrated to be proportional to nasal air flow, which allows calculation of apnoea hypopnea index (AHI).   Objective   To test if nasal pressure variation measurement increases accuracy of diagnosis of OSA than SPO 2  alone.   Method   31 patients with clinical features of OSA were enrolled. Their overnight nasal pressure variations were picked up by a microphone fixed the distal end of a nasal cannula. The microphone signal was processed with elimination of baseline noise, and airflow measurements were derived. Airflow was analyzed together with SPO 2  to calculate AHI.   Results    The Epworth sleepiness scale (ESS) of patients ranged 0 to 19 (mean 8) and Mallampati grade (MG) ranged 1 to 4 (mean 2). The mean BMI was 28.4 kg/m 2  (range 20.44 to 40.48). The oxygen desaturation index (ODI), the number of desaturations per hour, ranged 0 to 15 (mean 2). The mean AHI was 8 (range 0 to 40). AHI significantly correlated with ODI (Pearson correlation coefficient = .63 p= .00). 13 patients were diagnosed with OSA using AHI. ODI alone would result in 4 true positive, 9 false negative and 2 false positive diagnosis of OSA.   Conclusions   Nasal pressure variation measured by a microphone can be combined with SPO 2  to increase accuracy of diagnosis of OSA in patients with clinical likelihood, in a resource poor setting. With further validation this technique may be used for a low cost portable home based apparatus to derive AHI.
Serum S-100B Protein as a Prognostic Marker in Malignant Cutaneous Melanoma
Authors: E. Djureen Mårtenson, L.O. Hansson, B. Nilsson, E. von Schoultz, E. Månsson Brahme, U. Ringborg, J. Hansson
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate whether S-100B protein in serum is an independent prognostic marker in malignant melanoma. MATERIALS AND METHODS: S-100B protein in serum was analyzed in 1,007 consecutive patients with histologically verified cutaneous malignant melanoma. At the time of blood sampling, 876 patients were in clinical stage I, 35 were in stage II, and 96 were in stage III. The serum concentrations of S-100B protein were measured by a luminescence immunoassay (LIA). RESULTS: The mean serum concentration of S-100B protein was significantly related to clinical stage, with the lowest level in stage I and the highest in stage III. In a multivariate analysis, S-100B protein levels in serum showed the strongest prognostic impact of the factors analyzed with respect to disease-specific survival in clinical stages II to III, followed by clinical stage. Serum S-100B protein was not a significant independent prognostic factor in clinical stage I, where tumor thickness showed the strongest relation to melanoma-specific survival, followed by ulceration and satellites. CONCLUSION: This investigation contains the largest material of patients so far analyzed with the new LIA assay of S-100B protein in serum and confirms that S-100B protein in serum is correlated with clinical stage and is an independent prognostic marker in clinical stages II and III.
Hospitals send patients home without confirming home situation is adequate, report says
Authors: Ingrid Torjesen
Journal: BMJ (2015)

Vulnerable patients are being discharged from hospital unsafely and sent home to situations where they have inadequate support because of lack of coordination between health, social care, and community services, an investigation by the healthcare consumer organisation Healthwatch England has found.

The investigation was based on the experiences of discharge of 3230 people considered as vulnerable (elderly people, homeless people, and people with mental health conditions) and on information gathered from trusts through freedom of information legislation and from surveys of patients. It showed that although patients …
Cardiac toxicity of 5FU: Does prophylactic telemetry monitoring of patients at increased risk for cardiac toxicity improve safety? A 10-year experience
Authors: J. F. Pizzolato, M. S. Baum, R. M. Steingart, M. Gonan, B. D. Minsky, L. B. Saltz
Journal: Journal of Clinical Oncology (2004)

8107 Background: 5FU can cause cardiac toxicity as a result of induced coronary artery spasm. This risk appears to be amplified in patients with histories of coronary artery disease. Coronary vasospasm manifests as ST segment elevations during continuous ECG monitoring. The incidence of reported cardiac events has varied from less than 1% to as high as 8%. In the absence of established evidence-based guidelines, management practices vary. At our center selected patients felt to be at high risk have been prophylactically admitted to receive 5FU with inpatient telemetry monitoring. We now report a retrospective analysis of this practice. Our objectives were (1) to evaluate the incidence of cardiac events in high-risk patients admitted for telemetry during 5FU administration, and (2) to determine the utility of telemetry as a guide for coronary vasospasm in patients with cardiac risk. Methods: A retrospective chart review was conducted using the database at Memorial Sloan-Kettering Cancer Center to identify patients who received concurrent 5FU and telemetry as an inpatient between 10/93 and 1/03. Cardiac events were considered to be the development of any symptoms or telemetric ST changes consistent with vasospasm. Results: A total of 88 patients comprising of 463 telemetry days were evaluated. 82/88 (93%) patients had either 1 or more cardiac risk factors or a history of an arrhythmia or abnormal ECG. 3 patients were admitted for advanced age and 3 had no clearly identifiable risk factors. Of 88 patients, 4 patients (CI 1.2%–11.2%) developed chest pain while receiving 5FU. There were no patients in whom telemetric ST changes consistent with coronary vasospasm were found (CI 0–4.1%). In total, there were 0 events attributable to vasospasm in 463 telemetry days (CI 0–0.01 events/day) that were picked up by telemetry. Conclusions: Over a 10 year period, there were no patients in whom telemetry monitoring led to the detection of coronary vasospasm in selected high risk patients. Our experience does not support the routine use of elective telemetric monitoring in patients with significant cardiac risk factors receiving 5FU. No significant financial relationships to disclose.
World Trade Center fine particulate matter--chemistry and toxic respiratory effects: an overview.
Authors: Stephen H Gavett
Journal: Environmental Health Perspectives (2003)

The 11 September 2001 terrorist attack on New York City's World Trade Center (WTC) caused an unprecedented environmental emergency. The collapse of the towers sent a tremendous cloud of crushed building materials and other pollutants into the air of lower Manhattan. In response to the calamity, federal, state, and city environmental authorities and research institutes devoted enormous resources to evaluate the impact of WTC-derived air pollution on public health. Unfortunately, on the day of the disaster, no air-sampling monitors were operating close to the WTC site to characterize and quantify pollutants in the dust cloud. However, analysis of fallen dust samples collected 5 and 6 days after the attack showed that 1-4% by weight consisted of particles small enough to be respirable (Lioy et al. 2002). These particles included fine particulate matter, or PM(subscript)2.5(/subscript) [PM < 2.5 micro m mass median aerodynamic diameter (MMAD)], which can be inhaled deep into the lung and is associated with cardiovascular and respiratory health effects. Because of the extremely high concentrations of dust immediately after the collapse of the towers, even a relatively small proportion of PM(subscript)2.5(/subscript) in the dust clouds could have contributed to breathing problems in rescue workers and others who were not wearing protective masks.
Abstract 1037: Angiotensin II Type 1 Receptor 1166 Polymorphism A -> C Increases mRNA Stability and Steady-State Levels
Authors: Jukka Lehtonen, Kirsi Paukku, Laurent Daviet, Kimmo Kontula
Journal: Circulation (2006)

Angiotensin II type 1 receptor (AT1R) regulation plays an important role in the pathogenesis of hypertension and heart failure. Posttranscriptional regulation of AT1R is largely mediated by its 3′untranslated region (3′UTR). In order to analyze structure-function relationship of the 3′UTR, a number of AT1R 3′UTR constructs were created and tested. Removal of 3′UTR from AT1R message increases mRNA levels by increasing its half-life. Transfer of the 3′UTR of AT1R to 3′end of either bcl-2 or luciferase coding region resulted in a decrease in the steady-state mRNA expression of these fusion constructs and therefore 3′UTR contains all the necessary elements for its inhibitory effect. Functional characterization of 3′UTR deletions and domain swapping constructs showed that 3′UTR contains both stabilizing and destabilizing elements resulting in increased or decreased steady-state mRNA levels. In order to identify functionally active regions, AT1R 3′UTR was subjected to random mutagenesis. After several rounds of screening, two single base alterations were found to have an effect on mRNA levels. Alteration in the base at 1255 resulted in a 3-fold decrease and at 1166 2.5-fold increase in mRNA levels. Thus AT1R 3′UTR 1166 A → C polymorphism results in a partial loss of 3′UTR effect on mRNA destabilization. Interestingly, the carrier status of this single polymorphism located in the 3′UTR of AT1R has been associated with increased incidence of hypertension and higher rate of restenosis. In order to study the RNA-protein interactions, we performed RNA-shift and Northwestern assays using 3′UTR 1081–1181 as a probe and found at least three RNA-interacting proteins at sizes of 17 kDa, 35 kDa, and 45 kDa. It is tempting to speculate that changes in RNA-protein interactions could explain the effects of 1166 A → C polymorphism on mRNA levels.
Cold polypectomy for nonampullary duodenal adenoma
Authors: Daisuke Maruoka, Makoto Arai, Hideaki Ishigami, Kenichiro Okimoto, Tomoaki Matsumura, Tomoo Nakagawa, Osamu Yokosuka
Journal: Endoscopy (2015)

Cold polypectomy for colorectal polyps has been widely performed in Western countries and is now becoming widespread in Japan. Both cold forceps polypectomy (CFP) and cold snare polypectomy (CSP) are safe and efficient for colorectal polyps [1] [2]. These procedures are excellent in regard to safety, in particular because electrocautery is not needed; thus, perforation or delayed bleeding rarely occurs [1] [2]. However, there have been no reports of cold polypectomy for duodenal polyps.
Lymphocyte Responses to an Aqueous Extract from Cow Hair and Dander
Authors: P. Prahl, G. Sønderstrup Hansen
Journal: Allergy (1982)

The proliferative responsiveness to cow dander antigens of lymphocytes from 23 asthmatic patients with allergy to cow hair and dander, from 10 patients with allergic asthma to other antigens and from 31 non‐atopic subjects was investigated. Lymphocytes from patients with allergic asthma due to cow epithelium antigens showed a statistically significant decreased responsiveness to an extract from cow dander, compared to that seen with lymphocytes from newborn infants, lymphocytes from normal controls and from asthmatic patients without allergy to cow. The response to the cow dander extract seemed to be an accessory cell dependent T lymphocyte response.
Neurodegenerative disorders
Authors: R. Kale
Journal: BMJ (2001)

Inow begin the journey that will lead me into the sunset of my life,” was how Ronald Reagan described his remaining life.1 That was seven years ago when he told the world that he had Alzheimer's disease. The sunset has been a prolonged one, as is usual in most neurodegenerative disorders, of which Alzheimer's is a prototype. All have an insidious onset, progress slowly over years, and death is usually due to an intercurrent illness and not directly due to the disease itself. Predictably the global burden of diseases like Alzheimer's will rise with increasing longevity. Much of the burden is also borne by carers and relatives. Reagan's daughter, Maureen Reagan, summed up what the illness means to carers. “[Ronald's wife …