tbuckley/cabot-search huggingface dataset:
A confidential inquiry into asthma deaths in Wales
Authors: M L Burr, B H Davies, A Hoare, A Jones, I J Williamson, S K Holgate, R Arthurs, I G C Hodges
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Death from asthma is regarded as preventable in principle, especially under the age of 65 years. <h3>METHODS</h3> In 1994 a confidential inquiry was set up to investigate deaths attributable to asthma in residents of Wales under the age of 65 years. During the period of the inquiry 92 cases were notified as being ascribed to asthma, or (in 1996) having a mention of asthma on the death certificate. Of these, 80 were investigated further with the help of general practitioners, hospital notes, and relatives. The details were then considered by a small panel of doctors who endeavoured to identify factors that may have contributed to the deaths. <h3>RESULTS</h3> Asthma was considered to be the underlying cause of 52 deaths. Although disease severity was usually a major factor, some aspect of the patient's behaviour or circumstances seemed to have contributed to 31 deaths, while in 15 cases there was probably a deficiency in medical care. <h3>CONCLUSIONS</h3> Some preventable asthma deaths still occur, particularly in relation to inadequate treatment. Factors associated with patients' behaviour and circumstances are more difficult to tackle but, if doctors are aware of high risk patients, increased vigilance may prevent some deaths.
Acute results of the restenosis reduction by cutting balloon evaluation study
Authors: H. Hosckawa, T. Yamaguchi, T. Kobayashi, T. Muramatsu, H. Nishikawa, T. Inoue, T. Matsushita, H. Hirayama, T. Kondo, K. Kanemasa, M. Kijima, T. Suzuki
Journal: Journal of the American College of Cardiology (1998)
The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in mice
Authors: Qing-Jun Zhang, Hou-Zao Chen, Lin Wang, De-Pei Liu, Joseph A. Hill, Zhi-Ping Liu
Journal: Journal of Clinical Investigation (2011)

Cardiac hypertrophy and failure are accompanied by a reprogramming of gene expression that involves transcription factors and chromatin remodeling enzymes. Little is known about the roles of histone methylation and demethylation in this process. To understand the role of JMJD2A, a histone trimethyl demethylase, in cardiac hypertrophy, we generated mouse lines with heart-specific Jmjd2a deletion (hKO) and overexpression (Jmjd2a-Tg). Jmjd2a hKO and Jmjd2a-Tg mice had no overt baseline phenotype, but did demonstrate altered responses to cardiac stresses. While inactivation of Jmjd2a resulted in an attenuated hypertrophic response to transverse aortic constriction-induced (TAC-induced) pressure overload, Jmjd2a-Tg mice displayed exacerbated cardiac hypertrophy. We identified four-and-a-half LIM domains 1 (FHL1), a key component of the mechanotransducer machinery in the heart, as a direct target of JMJD2A. JMJD2A bound to the FHL1 promoter in response to TAC, upregulated FHL1 expression, and downregulated H3K9 trimethylation. Upregulation of FHL1 by JMJD2A was mediated through SRF and myocardin and required its demethylase activity. The expression of JMJD2A was upregulated in human hypertrophic cardiomyopathy patients. Our studies reveal that JMJD2A promotes cardiac hypertrophy under pathological conditions and suggest what we believe to be a novel mechanism for JMJD2A in reprogramming of gene expression involved in cardiac hypertrophy.
Celecoxib Can Prevent Tumor Growth and Distant Metastasis in Postoperative Setting
Authors: Jong-Lyel Roh, Myung-Whun Sung, Seok-Woo Park, Dae-Seog Heo, Dong Wook Lee, Kwang Hyun Kim
Journal: Cancer Research (2004)

Abstract Much evidence suggests that an inflammatory condition provides a microenvironment favorable for tumor growth. One of the main components in the healing wound is the induction of cyclooxygenase-2 (COX-2) and prostaglandins, and many solid tumors have been known to overexpress COX-2. The present study investigated the relationship between surgical wounds and tumor growth and the roles of COX-2 and inflammatory reaction in this microenvironment. We created surgical wounds in syngeneic mice for the implantation of SCC VII murine cancer cell line. Accelerated tumor growth and increased angiogenesis by surgical wounds were clearly observed in C3H/HeJ mice with SCC VII tumor. The COX-2 expression of peritumoral tissues and leukocyte infiltration partly explained the accelerated tumor growth, especially in the early phase after surgical wounding. Celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in tumor-implanted mice with surgical wounds. This tumor-suppressive action of celecoxib did not show any noticeable side effects on the late wound healing and on the gastrointestinal tracts. Prophylactic use of the drug can be advocated in many clinical situations, such as residual tumors or contamination of surgical fields by tumor cells.
Criteria for Optimizing Prognostic Risk Groups in Pediatric Cancer: Analysis of Data From the Children's Oncology Group
Authors: Richard Sposto, Wendy B. London, Todd A. Alonzo
Journal: Journal of Clinical Oncology (2007)

Physicians who treat cancer often attempt to identify patient subgroups that are homogeneous in their chance of recurrence or death as a way to target the more toxic and presumably more effective treatments to patients with the worst prognosis. However, to date, prognosis-based treatment assignment in pediatric cancer has not been based on a quantitative assessment of the risks and benefits of different treatment strategies or on morbidity and efficacy outcome measures that are relevant to children.We performed a quantitative analysis of the risks and benefits of prognosis-based treatment assignment in two examples from the Children's Oncology Group using a mathematical model of cancer cure and permanent treatment morbidity and defined an optimality criterion for assigning treatments to specific risk groups.In stage 4 MYCN-unamplified neuroblastoma, age-based risk grouping distinguishes clearly between patients with high and low risk of recurrence. However, our analysis suggests that the optimal age cut point depends profoundly on the morbidity of the treatments being considered and agrees with current published recommendations only for treatments that add significant morbidity. In Hodgkin's lymphoma, under our model, no clearly optimal risk groupings exist, and a compelling quantitative rationale for defining risks group at all may not exist.Our analysis illustrates the inadequacy of naïve application of statistical criteria for defining prognostic risk groups in pediatric cancer and highlights the importance of quantifying treatment morbidity when defining risk groups or when deciding whether risk grouping is warranted.
Is the portable NIOX MINO reliable for screening nasal nitric oxide levels in primary ciliary dyskinesia
Authors: Amanda Harris, Esther Bhullar, Rhiannon Joslin, Kerry Gove, Jane Lucas
Journal: European Respiratory Journal (2012)

BACKGROUND: Nasal nitric oxide (nNO) levels are very low in patients with PCD. nNO is used as a screening test for PCD. The portable NIOX MINO (Aerocrine, Sweden), is now able to make nasal measurements. This study aimed to assess the usability and reproducibility of the NIOX MINO measurements and comparison of MINO measurements with the 'standard' NIOX Flex.

METHODS: Paired MINO and Flex readings were taken from 22 participants (3 PCD, 5 asthma +/- rhinitis, 12 healthy, 1 CF, 1 nonCF/nonPCD lung disease; age 5-64years) nNO was measured using Flex.during breath holding, and using the Niox MINO using nasal aspiration at 2 and 5ml during mouth breathing, three times for each measurement.

RESULTS: One participate was unable to use Flex or MINO, one participant was able to obtain acceptable readouts using the MINO at 5ml/sec but not at 2ml/sec nor Flex. Younger children were able to obtain measurements at 5ml/sec but not 2ml/sec. Within-method there was good inter-patient reproducibility using the Flex and MINO. Between method, nNO levels using the MINO at 2ml/sec were comparable with Flex (p=0.098) but readings using the MINO at 5ml/sec were significantly lower than Flex (p<0.001). PCD patients had extremely low levels of nNO (<50ppb) independent of method. A patient with CF had very low nNO (<50ppb) using Flex and MINO (5ml/sec).

CONCLUSIONS: Patients who were able to use Flex could also provide nNO measurements using the MINO at 5ml/sec; younger children were unable to use it at 2ml/sec. Reproducibility of nNO within method was acceptable. Measurements using the MINO at 5ml/sec were low in comparison to Flex, but would still differentiate patients with PCD from healthy controls.
Are There Any Ethnic Differences in Molecular Predictors of Erlotinib Efficacy in Advanced Non-Small Cell Lung Cancer?
Authors: Myung-Ju Ahn, Byeong-Bae Park, Jin Seok Ahn, Sang We Kim, Heung-Tae Kim, Jong Seog Lee, Jin Hyung Kang, Jae Yong Cho, Hong Suk Song, Se Hoon Park, Chang Hak Sohn, Sang Won Shin, Jin Hyuck Choi, Chang-Seok Ki, Chan Keum Park, Alison J. Holmes, Pasi A. Jänne, Keunchil Park
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib. Experimental Design: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry. Results: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (γ = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P &amp;lt; 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P &amp;lt; 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89). Conclusions: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.
Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality
Authors: F.G.R. Fowkes, G.D. Murray, I. Butcher, C.L. Heald, R.J. Lee, L.E. Chambless, A.R. Folsom, A.T. Hirsch, M. Dramaix, G. deBacker, J.C. Wautrecht, M. Kornitzer, A.B. Newman, M. Cushman, K. Sutton-Tyrrell, A.J. Lee, J.F. Price, R.B. D'Agostino, J.M. Murabito, P.E. Norman, K. Jamrozik, J.D. Curb, K.H. Masaki, B.L. Rodriquez, J.M. Dekker, L.M. Bouter, R.J. Heine, G. Nijpels, C.D.A. Stehouwer, L. Ferrucci, H.E. Stoffers, J.D. Hooi, J.A. Knottnerus, M. Ogren, B. Hedblad, J.C. Witteman, M.M.B. Breteler, M.G.M. Hunink, A. Hofman, M.H. Criqui, R.D. Langer, A. Fronek, W.R. Hiatt, R. Hamman, H.E. Resnick, J. Guralnik, M.M. McDermott
Journal: JAMA (2008)

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Upregulation of cathepsin D in the caudate nucleus of primates with experimental parkinsonism
Authors: Sowmya V Yelamanchili, Amrita Datta Chaudhuri, Claudia T Flynn, Howard S Fox
Journal: Molecular Neurodegeneration (2011)

In Parkinson's disease there is progressive loss of dopamine containing neurons in the substantia nigra pars compacta. The neuronal damage is not limited to the substantia nigra but progresses to other regions of brain, leading to loss of motor control as well as cognitive abnormalities. The purpose of this study was to examine causes of progressive damage in the caudate nucleus, which plays a major role in motor coordination and cognition, in experimental Parkinson's disease.Using chronic 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine treatment of rhesus monkeys to model Parkinson's disease, we found a upregulation of Cathepsin D, a lysosomal aspartic protease, in the caudate nucleus of treated monkeys. Immunofluorescence analysis of caudate nucleus brain tissue showed that the number of lysosomes increased concurrently with the increase in Cathepsin D in neurons. In vitro overexpression of Cathepsin D in a human neuroblastoma cell line led to a significant increase in the number of the lysosomes. Such expression also resulted in extralysosomal Cathepsin D and was accompanied by significant neuronal death associated with caspase activation. We examined apoptotic markers and found a strong correlation of Cathepsin D overexpression to apoptosis.Following damage to the substantia nigra resulting in experimental Parkinson's disease, we have identified pathological changes in the caudate nucleus, a likely site of changes leading to the progression of disease. Cathepsin D, implicated in pathogenic mechanisms in other disorders, was increased, and our in vitro studies revealed its overexpression leads to cellular damage and death. This work provides important clues to the progression of Parkinson's, and provides a new target for strategies to ameliorate the progression of this disease.
Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: U.S. Food and Drug Administration Drug Approval Summary
Authors: Paul G. Kluetz, Yang-Min Ning, V. Ellen Maher, Lijun Zhang, Shenghui Tang, Debasis Ghosh, Robeena Aziz, Todd Palmby, Elimika Pfuma, Jeanne Fourie Zirkelbach, Nitin Mehrotra, Amy Tilley, Rajeshwari Sridhara, Amna Ibrahim, Robert Justice, Richard Pazdur
Journal: Clinical Cancer Research (2013)

On December 10, 2012, the U.S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P < 0.0001}. A prespecified interim analysis demonstrated an improvement in OS favoring the abiraterone acetate arm [HR, 0.79 (95% CI, 0.66-0.96)] but did not cross the O'Brien-Fleming boundary for statistical significance. Safety data confirmed the known adverse reaction profile of abiraterone acetate. Full approval was granted on the basis of a large magnitude of effect on rPFS, a favorable trend in OS, and internal consistency across multiple secondary endpoints and exploratory patient-reported pain data. This is the first drug approval for mCRPC to use rPFS as the primary endpoint. Importantly, this approval was granted in the context of a prior statistically significant OS benefit that formed the basis of the original April 28, 2011, approval of abiraterone acetate for patients with mCRPC who had received prior chemotherapy containing docetaxel.
Evaluation Of The Immunological Mechanisms Involved In The Efficacy Of Sublingual Immunotherapy With Ltp (Pru p 3) In Allergic Patients Sensitized To Food By Ltps
Authors: Francisca Gomez, Enrique Gomez, Maria J. Torres, Luisa Galindo, Maria Dolores Ruiz, Inmaculada Doña, Gador Bogas, Paloma Campo, Teresa Posadas, Miguel Blanca, Cristobalina Mayorga
Journal: Journal of Allergy and Clinical Immunology (2014)
Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel
Authors: K. Shitara, K. Matsuo, D. Takahari, T. Yokota, T. Shibata, T. Ura, S. Ito, A. Sawaki, M. Tajika, H. Kawai, K. Muro
Journal: Annals of Oncology (2010)
Controversies in neuro-oncology: does valganciclovir have a role in the treatment of high-grade gliomas?
Authors: P. Y. Wen
Journal: Neuro-Oncology (2014)

Human cytomegalovirus (CMV) is a common herpes virus trophic for glial cells with a seroprevalence of 50-90% in adult population.1–3 In 2002, Dr. Charles Cobbs and colleagues reported that a high percentage of gliomas were infected with CMV and multiple CMV gene products were expressed in these tumors.3 Since then there has been controversy related to the role of CMV in the pathogenesis of gliomas, and whether it represents a potential therapeutic target. This controversy has intensified recently with the publication of a letter in the New England Journal of Medicine by Soderberg-Naucler and colleagues who performed a retrospective analysis of a previously published negative randomized phase II study of adjuvant valganciclovir in newly-diagnosed glioblastomas (Valcyte Treatment of Glioblastoma Patients in Sweden (VIGAS) study).4,5 In this analysis they found that a subset of patients who received more than 6 months of therapy with valganciclovir had significantly prolonged survival compared to contemporary controls.4 Analysis of a larger group of 50 patients treated both within the VIGAS trial and on compassionate basis also suggested improved outcome.4 These results have led to significant interest with in the neuro-oncology community, and especially among patients, regarding the potential value of valganciclovir and other anti-CMV therapies for high-grade gliomas. In the subsequent articles, one by Dr. Charles Cobbs and another by Drs. Wolfgang Wick and Michael Platten, the authors discuss the data regarding the role of CMV in high-grade gliomas and whether anti-CMV therapies such as valganciclovir have a therapeutic role.
Vasomotion in Venous Disease
Authors: T R Cheatle, S K Shami, E Stibe, P D Coleridge Smith, J H Scurr
Journal: Journal of the Royal Society of Medicine (1991)

Abnormalities of the capillary microcirculation may be important in the pathogenesis of venous ulceration. In this study the characteristics of capillary vasomotion in venous disease have been studied using laser Doppler flowmetry. The amplitude and frequency of vasomotion in the skin microcirculation as measured by laser Doppler flowmetry was determined in 101 subjects. These comprised 43 subjects with venous disease and lipodermatosclerosis (LDS), 14 subjects with uncomplicated varicose veins (VV), and 44 normal controls. In 43 of these 101 limbs, vasomotion was also measured after heating the skin to 43 degrees C. The resting laser Doppler flux was significantly higher in the LDS group compared to the other two groups (LDS median = 76, VV median = 47 (P less than 0.04), controls median = 49 (P less than 0.003]. The amplitude of vasomotive waves was significantly higher in the LDS group compared to controls (LDS median = 20, VV median = 8.3 (P less than 0.007), controls median = 14 (P less than 0.007), as was the frequency of vasomotion (LDS median = 3.3 waves/min, VV median = 2.5 (P = ns), controls median = 2.7 (P less than 0.007]. On heating the skin to 43 degrees C the frequency of the vasomotion increased significantly in the control (P less than 0.004) and VV (P less than 0.04) groups but not in the LDS group. The amplitude of the vaso-motion also increased significantly in the control (P less than 0.01) and VV (P less than 0.002) groups but not in the LDS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Out-of-Hospital Pediatric Endotracheal Intubation on Survival and Neurological Outcome
Authors: Marianne Gausche, Roger J. Lewis, Samuel J. Stratton, Bruce E. Haynes, Carol S. Gunter, Suzanne M. Goodrich, Pamela D. Poore, Maureen D. McCollough, Deborah P. Henderson, Franklin D. Pratt, James S. Seidel
Journal: JAMA (2000)

Context Endotracheal intubation (ETI) is widely used for airway management of children in the out-of-hospital setting, despite a lack of controlled trials demonstrating a positive effect on survival or neurological outcome.Objective To compare the survival and neurological outcomes of pediatric patients treated with bag-valve-mask ventilation (BVM) with those of patients treated with BVM followed by ETI.Design Controlled clinical trial, in which patients were assigned to interventions by calendar day from March 15, 1994, through January 1, 1997.Setting Two large, urban, rapid-transport emergency medical services (EMS) systems.Participants A total of 830 consecutive patients aged 12 years or younger or estimated to weigh less than 40 kg who required airway management; 820 were available for follow-up. InterventionsPatients were assigned to receive either BVM (odd days; n = 410) or BVM followed by ETI (even days; n = 420). Main Outcome MeasuresSurvival to hospital discharge and neurological status at discharge from an acute care hospital compared by treatment group. ResultsThere was no significant difference in survival between the BVM group (123/ 404 [30%]) and the ETI group (110/416 [26%]) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.61-1.11)or in the rate of achieving a good neurological outcome (BVM, 92/404 [23%] vs ETI, 85/416 [20%]) (OR, 0.87; 95% CI, 0.62-1.22). ConclusionThese results indicate that the addition of out-of-hospital ETI to a paramedic scope of practice that already includes BVM did not improve survival or neurological outcome of pediatric patients treated in an urban EMS system.