tbuckley/cabot-search huggingface dataset:
Bronchial asthma on Mount Kilimanjaro is not a disadvantage
Authors: S Stokes, N Kalson, M Earl, H Frost, A G Whitehead, I Tyrrell-Marsh, A Davies
Journal: Thorax (2008)

Bronchial asthma on Mount Kilimanjaro is not a disadvantageEvery year, an increasing number of people travel to high altitude and travellers with asthma are becoming more common in remote environments. 1It is well recognised that certain situations at high altitude, such as exercising in cold air, may provoke symptoms. 2However, the mountain
NOTES ON PENETRATING WOUNDS OF THE BRAIN
Authors: H. Cushing
Journal: BMJ (1918)

IN the latel part of July tliree conitiguons casualty clearing stations in a certain arimjy area were desigiated as a centa'e for tile reception of all wounds of tile head occurring duirinig an expected period of military activity.To one of thiese liospitals the wi-iter was attachied for thiree months, and on takinia up hiis duties endeavoured to iilalae an estimate of wilat maiolit be:1. TIle operation mortality at all tllree hiospitals cotlibined.
Effects of partial truncal vagotomy on intragastric pressure responses to vagal stimulation and gastric distension in ferrets.
Authors: S A Asala, A J Bower, I N Lawes
Journal: Gut (1987)

Changes in intragastric pressure after dorsal truncal vagotomy, investigated by stimulation of the surviving vagal branches and by step inflation of the stomach, were divided into an early phase lasting five days, and a late phase continuing for at least three months. During the early phase the amplitude of vagal evoked contraction was diminished but the resting pressure and the response to gastric inflation were increased. After the fifth day vagal evoked contractions doubled in amplitude but the resting pressure and the response to step inflation of the stomach returned to control levels. Ventral vagotomy did not produce any substantial changes. Alterations to gastric and body weight, or to the relation between resting pressure and evoked contraction and relaxation were excluded as causes of the enhanced vagal effectiveness. Sprouting of axons into denervated territory occurred too late to explain the changes, but an increase in synaptic density within the innervated territory has not been ruled out.
Global access to surgical care: a modelling study
Authors: Blake C Alkire, Nakul P Raykar, Mark G Shrime, Thomas G Weiser, Stephen W Bickler, John A Rose, Cameron T Nutt, Sarah L M Greenberg, Meera Kotagal, Johanna N Riesel, Micaela Esquivel, Tarsicio Uribe-Leitz, George Molina, Nobhojit Roy, John G Meara, Paul E Farmer
Journal: The Lancet Global Health (2015)

More than 2 billion people are unable to receive surgical care based on operating theatre density alone. The vision of the Lancet Commission on Global Surgery is universal access to safe, affordable surgical and anaesthesia care when needed. We aimed to estimate the number of individuals worldwide without access to surgical services as defined by the Commission's vision.
Regional cardiac prostaglandin release during myocardial ischemia in anesthetized dogs.
Authors: H J Berger, B L Zaret, L Speroff, L S Cohen, S Wolfson
Journal: Circulation Research (1976)

Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in seven dogs. Samples were assayed for prostaglandins F, E, and A by randioimmunoassay. All dogs demonstrated prostaglandin F release, Mean +/- SE postocclusion aortic levels were 0.26 +/- 0.01 ng/ml; coronary sinus levels were 0.67 +/- 0.01 ng/ml (P less than 0.001). In six dogs, prostaglandin E also was released. Mean postocclusion aortic levels were 0.24 +/- 0.01 ng/ml; coronary sinus, 0.44 +/- 0.01 ng/ml (P less than 0.001). There was no release of prostaglandin A. To examine the site of prostaglandin release, simultaneous samples from the aorta, the coronary sinus, and the great cardiac vein were obtained before and after left circumflex artery occlusion in six additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All six dogs demonstrated prostaglandin F release from the ischemic region. Mean postocclusion aortic prostaglandin F was 0.32 +/- 0.01 ng/ml. Coronary sinus prostaglandin F was 1.69 +/- 0.03 ng/ml (P less than 0.001), whereas the great cardiac vein level remained at 0.34 +/- 0.01 ng/ml (P greater than 0.05). Prostaglandin E was released from both ischemic and nonischemic regions. Mean aortic prostaglandin E was 0.21 +/- 0.01 ng/ml; great cardiac vein, 0.55 +/- 0.02 ng/ml (P less than 0.001); and coronary sinus, 1.07 +/- 0.04 ng/ml (P less than 0.001). These results have led us to conclude that the different local availability of prostaglandins E and F may influence the cardiac response to ischemia.
Osteoporosis in adults with cystic fibrosis
Authors: C S Haworth, P L Selby, A K Webb, J E Adams
Journal: Journal of the Royal Society of Medicine (1998)

Osteoporosis is prevalent in adults with CF Longitudinal data have not been collected and so the natural history is unknown. The aetiology is not known. There are no published randomized controlled trials evaluating treatments for osteoporosis in CF patients.
P2 Outbreak case definitions for extrinsic allergic alveolitis due to metalworking fluids
Authors: C. Burton, P. Burge, A. Robertson, W. Robertson, C. Pickering, D. Hendrick, C. Barber
Journal: Thorax (2010)

<h3>Introduction</h3> In 2003, a large outbreak of occupational lung disease (OLD) occurred in the Powetrain plant in Birmingham, which included 21 workers who met the case definition for extrinsic allergic alveolitis (EAA). The aim of this study was to assess the performance of the case definition used during this and other outbreaks, against best available clinical diagnosis. <h3>Methods</h3> All available hospital clinical data (including follow-up) for 37 workers with a documented clinical suspicion of EAA during the outbreak investigation was reviewed by a panel meeting of 5 UK OLD specialists. A definite clinical EAA case was accepted if at least four of the five experts agreed. This opinion was compared with a range of case definitions previously used during UK and US outbreaks. <h3>Results</h3> A definite clinical diagnosis of EAA was accepted for 14 of the 37 workers. The performance (level of agreement, sensitivity and specificity) of different EAA case definitions vs the specialist clinical opinion is shown in Abstract P2 Table 1. <h3>Discussion</h3> The EAA case definition used in the Powertrain outbreak (Robertson 2007) showed substantial agreement with expert clinical opinion, correctly classifying 30/37 workers, without missing any of the definite clinical EAA cases. The Fox and Dangman criteria also performed well, correctly classifying a similar proportion of workers, but missing 1 and 3 of the definite clinical EAA cases respectively.
A Genome-Wide Search for Signals of High-Altitude Adaptation in Tibetans
Authors: S. Xu, S. Li, Y. Yang, J. Tan, H. Lou, W. Jin, L. Yang, X. Pan, J. Wang, Y. Shen, B. Wu, H. Wang, L. Jin
Journal: Molecular Biology and Evolution (2010)

Genetic studies of Tibetans, an ethnic group with a long-lasting presence on the Tibetan Plateau which is known as the highest plateau in the world, may offer a unique opportunity to understand the biological adaptations of human beings to high-altitude environments. We conducted a genome-wide study of 1,000,000 genetic variants in 46 Tibetans (TBN) and 92 Han Chinese (HAN) for identifying the signals of high-altitude adaptations (HAAs) in Tibetan genomes. We discovered the most differentiated variants between TBN and HAN at chromosome 1q42.2 and 2p21. EGLN1 (or HIFPH2, MIM 606425) and EPAS1 (or HIF2A, MIM 603349), both related to hypoxia-inducible factor, were found most differentiated in the two regions, respectively. Strong positive correlations were also observed between the frequency of TBN-dominant haplotypes in the two gene regions and altitude in East Asian populations. Linkage disequilibrium and further haplotype network analyses of world-wide populations suggested the antiquity of the TBN-dominant haplotypes and long-term persistence of the natural selection. Finally, a "dominant haplotype carrier" hypothesis could describe the role of the two genes in HAA. All of our population genomic and statistical analyses indicate that EPAS1 and EGLN1 are most likely responsible for HAA of Tibetans. Interestingly, one each but not both of the two genes were also identified by three recent studies. We reanalyzed the available data and found the escaped top signal (EPAS1) could be recaptured with data quality control and our approaches. Based on this experience, we call for more attention to be paid to controlling data quality and batch effects introduced in public data integration. Our results also suggest limitations of extended haplotype homozygosity-based method due to its compromised power in case the natural selection initiated long time ago and particularly in genomic regions with recombination hotspots.
Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells
Authors: Lara H. El Touny, Anthony Vieira, Arnulfo Mendoza, Chand Khanna, Mark J. Hoenerhoff, Jeffrey E. Green
Journal: Journal of Clinical Investigation (2013)

Breast cancer (BC) can recur as metastatic disease many years after primary tumor removal, suggesting that disseminated tumor cells survive for extended periods in a dormant state that is refractory to conventional therapies. We have previously shown that altering the tumor microenvironment through fibrosis with collagen and fibronectin deposition can trigger tumor cells to switch from a dormant to a proliferative state. Here, we used an in vivo preclinical model and a 3D in vitro model of dormancy to evaluate the role of Src family kinase (SFK) in regulating this dormant-to-proliferative switch. We found that pharmacological inhibition of SFK signaling or Src knockdown results in the nuclear localization of cyclin-dependent kinase inhibitor p27 and prevents the proliferative outbreak of dormant BC cells and metastatic lesion formation; however, SFK inhibition did not kill dormant cells. Dormant cell proliferation also required ERK1/2 activation. Combination treatment of cells undergoing the dormant-to-proliferative switch with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis in a large fraction of the dormant cells and delayed metastatic outgrowth, neither of which was observed with either inhibitor alone. Thus, targeting Src prevents the proliferative response of dormant cells to external stimuli, but requires MEK1/2 inhibition to suppress their survival. These data indicate that treatments targeting Src in combination with MEK1/2 may prevent BC recurrence.
Identification of a Novel Prostate Tumor Target, Mindin/RG-1, for Antibody-Based Radiotherapy of Prostate Cancer
Authors: Renate Parry, Doug Schneider, Debra Hudson, Debbie Parkes, Jian-Ai Xuan, Alicia Newton, Pam Toy, Rick Lin, Rick Harkins, Bruno Alicke, Sandra Biroc, Peter J. Kretschmer, Meredith Halks-Miller, Helmut Klocker, Ying Zhu, Brent Larsen, Ronald R. Cobb, Peter Bringmann, Georg Roth, Jason S. Lewis, Harald Dinter, Gordon Parry
Journal: Cancer Research (2005)

Gene expression analysis showed that a human mindin homologue, mindin/RG-1, is expressed selectively in prostate tissues and that its expression level is elevated in some prostate tumors. Mindin/RG-1 protein expression is maintained in >80% of prostate cancers metastatic to bone or lymph nodes as well as in locally recurrent tumors in androgen-unresponsive patients. In contrast, mindin/RG-1 expression in other normal tissues is significantly lower than that seen in the prostate. A fully human antibody, 19G9, was generated against mindin/RG-1 protein and was shown to accumulate at high abundance in LNCaP tumor xenografts. Conjugates of this antibody with the chelator CHX-A''-DTPA were generated and radiolabeled with either 111In, 90Y, or 86Y. Small animal positron emission tomography imaging with the 86Y-radiolabeled conjugate showed very specific accumulation of the antibody in LNCaP tumor xenografts with clear tumor delineation apparent at 4 hours. The therapeutic efficacy of [90Y]-CHX-A''-DTPA-19G9 was evaluated in mice bearing LNCaP xenografts. A dose-finding study identified a nontoxic therapeutic dose to be approximately 75 microCi. Significant antitumor effects were seen with a single administration of radiolabeled antibody to animals bearing 200 to 400 mm3 tumors. Inhibition of tumor growth was observed in all treated animals over a 49-day period. At 49 days posttreatment, slow tumor growth recurred but this could be prevented for an additional 40-day period by a second administration of a 75 microCi dose at day 49. We conclude that [90Y]-CHX-A''-DTPA-19G9 is a novel antibody conjugate that has considerable promise for therapy of metastatic prostate cancer in androgen-unresponsive patients.
Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype
Authors: Kyung Hee Noh, Young-Ho Lee, Ju-Hong Jeon, Tae Heung Kang, Chih-Ping Mao, T.-C. Wu, Tae Woo Kim
Journal: Cancer Research (2012)

Due to the exquisite specificity and potency of the immune system, vaccination is in theory the most precise and powerful approach for controlling cancer. However, current data from clinical trials indicate that vaccination rarely yields significant benefits for cancer patients in terms of tumor progression and long-term survival. The poor clinical outcomes of vaccination are primarily caused by mechanisms of immune tolerance, especially within the tumor microenvironment. Here, we report that vaccination drives the evolution of tumor cells toward an immune-resistant and stem-like phenotype that promotes tumor growth and nullifies the CTL response. The emergence of this phenotype required the transcription factor Nanog, which is induced as a consequence of immune selection. Nanog expression enhanced the stem-like features of tumor cells and protected them from killing by tumor-reactive CTLs. Delivery of siNanog into tumor-bearing mice rendered the tumor vulnerable to immune surveillance and strongly suppressed its growth. Together, our findings show tumor adaptation to vaccination through gain of an immune-resistant, stem-like phenotype and identify Nanog as a central molecular target in this process. Future vaccination technology should consider Nanog an important target to enhance the immunotherapeutic response.
Fatal aseptic meningoencephalitis following infliximab treatment for inflammatory bowel disease
Authors: R Quispel
Journal: Gut (2006)

Tumour necrosis factor α (TNF-α) plays a pivotal role in the pathogenesis of Crohn’s disease. Infliximab, a chimeric monoclonal antibody against TNF-α, has been shown to be highly effective in the treatment of Crohn’s disease.1 However, treatment with infliximab may give rise to serious adverse events, including autoimmune disorders.2 We report a case of fatal aseptic meningitis associated with infliximab therapy.

A 53 year old Caucasian man was admitted to a regional hospital with progressive bloody diarrhoea. His medical history revealed a myocardial infarction in 1993. Endoscopy and histology established a diagnosis inflammatory bowel disease (IBD) but could not distinguish between ulcerative colitis and Crohn’s disease. Because his symptoms did not improve following steroid and azathioprine treatment, infliximab therapy was initiated. Six days after the initial infliximab infusion, temporary numbness of …
Genomics and the challenging translation into conservation practice
Authors: Aaron B.A. Shafer, Jochen B.W. Wolf, Paulo C. Alves, Linnea Bergström, Michael W. Bruford, Ioana Brännström, Guy Colling, Love Dalén, Luc De Meester, Robert Ekblom, Katie D. Fawcett, Simone Fior, Mehrdad Hajibabaei, Jason A. Hill, A. Rus Hoezel, Jacob Höglund, Evelyn L. Jensen, Johannes Krause, Torsten N. Kristensen, Michael Krützen, John K. McKay, Anita J. Norman, Rob Ogden, E. Martin Österling, N. Joop Ouborg, John Piccolo, Danijela Popović, Craig R. Primmer, Floyd A. Reed, Marie Roumet, Jordi Salmona, Tamara Schenekar, Michael K. Schwartz, Gernot Segelbacher, Helen Senn, Jens Thaulow, Mia Valtonen, Andrew Veale, Philippine Vergeer, Nagarjun Vijay, Carles Vilà, Matthias Weissensteiner, Lovisa Wennerström, Christopher W. Wheat, Piotr Zieliński
Journal: Trends in Ecology & Evolution (2014)
Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison
Authors: Peter M Rothwell, Matthew F Giles, Arvind Chandratheva, Lars Marquardt, Olivia Geraghty, Jessica NE Redgrave, Caroline E Lovelock, Lucy E Binney, Linda M Bull, Fiona C Cuthbertson, Sarah JV Welch, Shelley Bosch, Faye Carasco-Alexander, Louise E Silver, Sergei A Gutnikov, Ziyah Mehta
Journal: The Lancet (2007)
Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial
Authors: Elton R. Kisanga, Jennifer Gjerde, Aliana Guerrieri-Gonzaga, Francesca Pigatto, Adriana Pesci-Feltri, Chris Robertson, Davide Serrano, Giuseppe Pelosi, Andrea Decensi, Ernst A. Lien
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG). Experimental Design: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67. Results: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n = 38, 37, and 36) were 7.5 (2.9–120.9), 25.2 (1.9–180.9), and 83.6 (8.7–134.4) in serum, and 78.2 (35.9–184), 272.3 (122–641), and 744.4 (208.6–2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. Conclusions: Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a &amp;gt;10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.
Advancing Continuing Medical Education
Authors: Graham T. McMahon
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Action plans for COPD self-management. Integrated care is more than the sum of its parts
Authors: M. D. L. Morgan
Journal: Thorax (2011)

The past few years have seen significant changes in attitude in many countries towards the care of people with chronic obstructive pulmonary disease (COPD). These changes have been driven by a greater understanding of the disease and the nature of its impact. Although there have been no new therapies that can modify the course of airway obstruction, there have been considerable advances in the way that we can lessen the impact of the disease on both the patient and the health community. There has clearly been a desire to improve the lives of individual people with COPD, but the major catalyst for change has probably been the desire of commissioners to reduce the cost of unnecessary hospital admissions resulting from exacerbation. To this end, the development of admission avoidance schemes has stimulated integrated community care programmes and importantly the involvement of the patient through a process known as self-management. The constituents of published self-management programmes vary quite widely, but most contain an action plan in the form of a set of instructions to inform the patient how to recognise an exacerbation and act accordingly. This is usually presented in a written format but can be pictorial if there are language difficulties or literacy issues.1 If they are also armed with treatment in the form of steroids and antibiotics, then it would be hoped that prompt action by the patient would then attenuate the serious exacerbation that would otherwise result in a hospital admission. The article by Trappenburg2 in this month's journal sheds further light on the …