tbuckley/cabot-search huggingface dataset:
Control of the Uptake of Oxygen
Authors: J. Hedley-Whyte
Journal: New England Journal of Medicine (1968)

DURING the last few years mechanical systems that can control the delivery of oxygen to the lungs have attained widespread use in medicine. Technics for measuring both the amount of oxygen delivered to the upper airways and the level actually within arterial blood have also recently become standardized. This discussion of the control of oxygen uptake will first concentrate on the basic principles of systems frequently used for the delivery of oxygen to the lungs and will then proceed to an analysis of the factors affecting oxygen uptake and the derangements of physiology that prevent oxygen from reaching arterial blood. . . .
Abstract B16: Phenotypic plasticity in the EML cell culture system as a result of HSP90 inhibition
Authors: Jennifer Napper, Vincent E. Sollars
Journal: Cancer Research (2013)

Abstract The process of canalization whereby phenotypic traits are buffered against stochastic fluctuations to preserve the evolutionarily advantageous “normal” level can be potentially exploited during cancer progression. Release of canalization through pharmacologic or genetic down-regulation of Hsp90 removes this buffer and increases variation, allowing for rapid changes in traits as evidenced in Drosophila, Arabidopsis, and maize. If cancer is viewed as a Darwinian struggle of the premalignant cell to acquire the hallmarks of a fully malignant cell or be extinguished, then increasing variation or heterogeneity has a beneficial effect on the fitness of the premalignant cell. It is the goal of this work to test the hypothesis that Hsp90-derived canalization, though its ability to buffer phenotypic variance and thus reduce cell plasticity, is involved in hematopoietic cell differentiation. Furthermore, we wish to determine if the canalization mechanism has an epigenetic component. We are currently using a murine hematopoietic stem cell culture system, EML cells, to investigate this hypothesis. EML cells have been induced to differentiate into macrophage and granulocyte lineages with and without pharmacologic inhibition of HSP90 through 17-AAG. We found that 17-AAG treatment increases the ability of these differentiating cells to survive in a selective medium, during culturing conditions that suggest an epigenetic mechanism. If our hypothesis is true, then loss of canalization could be a potentially powerful mechanism driving cancer progression. Fully understanding the mechanism involved would allow for new therapeutic insights and provide vital information regarding the use of HSP90 inhibitors. Citation Format: Jennifer Napper, Vincent E. Sollars. Phenotypic plasticity in the EML cell culture system as a result of HSP90 inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B16.
You're Never Too Old
Authors: John B. Wong, Deeb N. Salem, Stephen G. Pauker
Journal: New England Journal of Medicine (1993)

The Clinical Problem-Solving article “Too Old for What?” elsewhere in this issue1 describes an 87-year-old woman with severe aortic stenosis, three-vessel coronary artery disease, depressed left ventricular function, and moderately severe heart failure. Once the diagnosis of aortic stenosis was made, neither the patient's physicians nor the discussant considered nonsurgical therapy, but in an accompanying note the editor wonders whether the discussion, which strongly favors surgery, might be too one-sided. Might the risks of surgery outweigh the expected benefit of symptomatic improvement? Should the possibility of improved life expectancy have a role in such decisions? How should the potential for . . .
Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy
Authors: L. Qin, B. D. Smith, H. L. Tsai, N. K. Yaghi, P. H. Neela, M. Moake, J. Fu, Y. L. Kasamon, G. T. Prince, M. Goswami, G. L. Rosner, H. I. Levitsky, C. S. Hourigan
Journal: Blood Cancer Journal (2013)

The ability to target myeloid leukemia with immunotherapy would represent a significant therapeutic advance. We report here immunological analysis of clinical trials of primary and secondary vaccination with K562/GM-CSF immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP) with suboptimal responses to imatinib mesylate. Using serological analysis of recombinant cDNA expression libraries of K562 with autologous vaccinated patient serum, we have identified 12 novel chronic myeloid leukemia-associated antigens (LAAs). We show that clinical responses following K562/GM-CSF vaccination are associated with induction of high-titer antibody responses to multiple LAAs. We observe markedly discordant patterns of baseline and induced antibody responses in these identically vaccinated patients. No single antigen was recognized in all responses to vaccination. We demonstrate that an additional 'booster' vaccination series can be given safely to those with inadequate responses to initial vaccination, and is associated with more frequent induction of IgG responses to antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally, those with induced immune responses to the same LAAs often shared HLA subtypes and patients with clinical responses following vaccination recognized a partially shared but non-identical spectrum of antigens; both findings have potentially significant implications for cancer vaccine immunotherapy.
Immunogenicity of Whole-Parasite Vaccines against Plasmodium falciparum Involves Malarial Hemozoin and Host TLR9
Authors: Cevayir Coban, Yoshikatsu Igari, Masanori Yagi, Thornik Reimer, Shohei Koyama, Taiki Aoshi, Keiichi Ohata, Toshihiro Tsukui, Fumihiko Takeshita, Kazuo Sakurai, Takahisa Ikegami, Atsushi Nakagawa, Toshihiro Horii, Gabriel Nuñez, Ken J. Ishii, Shizuo Akira
Journal: Cell Host & Microbe (2010)
Abstract 1914: Molecular function of the long noncoding RNA SPRY4-IT1 in human melanomas.
Authors: Wei Zhao, Joseph Mazar, Jian-Liang Li, Lawrence M. Brill, Maya Ratnam, Ahmad M. Khalil, John S. Mattick, Marcel E. Dinger, Ranjan J. Perera
Journal: Cancer Research (2013)

Abstract Recently, we reported that the long noncoding RNA (lncRNA) SPRY4-IT1, which lies within the intronic region of the Sprouty4 gene, is upregulated in human melanomas and influences cell growth, proliferation, and motility, suggesting it may play an important role in the molecular etiology of human melanomas. Here, we report the identification of the full-length of SPRY4-IT1 transcript and its molecular function in human melanoma cells. SPRY4-IT1 transcripts are predominantly found in cytoplasm and accumulate in the polysome fraction of the cell suggests that they may interact with cellular proteins and/or interact with mRNAs to modulate the protein translation. We have identified a group of SPRY4-IT1 interacting proteins by isolating SPRY4-IT1 and protein binding complex and further characterization by mass spectrometry analysis. When SPRY4-IT1 ectopically expressed in melanocytes, it induced formation of multinucleated giant cells and modulates the expression of many genes including a subset of anti-apoptotic, cell cycle regulatory, DNA packaging, chromosome organization and chromatin architecture genes. Notably, the downregulation of the tumor suppressor gene dipeptidyl peptidase IV (DPPIV) and the upregulation the cellular proliferation marker Ki67 indicates the relevance of SPRY4-IT1 in the transition of melanocytes to melanomas. Citation Format: Wei Zhao, Joseph Mazar, Jian-Liang Li, Lawrence M. Brill, Maya Ratnam, Ahmad M. Khalil, John S. Mattick, Marcel E. Dinger, Ranjan J. Perera. Molecular function of the long noncoding RNA SPRY4-IT1 in human melanomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1914. doi:10.1158/1538-7445.AM2013-1914 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Infarct size measurement.
Authors: P J Boor
Journal: Circulation (1979)

First, in figure 4, the authors present the weighted tolerance limits about the regression lines according to Miller.'However, this technique is not mentioned in the reference given by the authors.Only unweighted tolerance limits are discussed.We would ap- preciate if the authors could give us a more pertinent reference on this topic.Second, in the Methods section, the authors state that variation about the regression line is a function of the body surface area, thus justifying the use of the weighted regression model.However, they do not describe how this function was estimated.The reference given2 does not discuss this.Again, we would be glad if the authors could provide us with some references on this subject.Finally, in order to determine the existence of such functions relating body surface area to variation about the regression line, we found the coordinates of the points appearing on three graphs of figure 4 (RVAWD, RVDD and PAD), by making photographic enlargements.The residuals were then analyzed for the three variables according to the techniques of Draper and Smith.2It was found that the variation about the regression line was not a function of the body surface area.Unweighted regression seemed then adequate.Moreover, the unweighted regression technique gave the same regression lines as those found by the authors, but the goodness of fit was far less.Table 1 shows the value of the multiple squared correlation coefficients found by using the unweighted regression technique compared to those calculated by the weighted regression technique of the authors.In conclusion, unless adequate answers can be given to the problems we have discussed, we are forced to consider that the regressions shown are questionable and that the validity of the con- clusions drawn can be seriously doubted.
Expression of differentiation antigens in benign sweat gland tumours
Authors: A.-L. KARINIEMI, L.M. FORSMAN, T. WAHLSTROM, L.C. ANDERSSON
Journal: British Journal of Dermatology (1984)

Fifty benign sweat gland tumours were studied for the expression of carcinoembryonic antigen (CEA) and apocrine epithelial antigen (AEA), using immunohistochemical methods. CEA was found in thirty-two and AEA in thirty-three neoplasms. Both antigens were located in the epithelium of the luminal structures and in the intraluminar material and CEA was occasionally found also in proliferating cells. Co-expression of CEA and AEA occurred frequently in cases of syringoma, syringocystadenoma papilliferum, hidradenoma papilliferum, eccrine spiradenoma and clear cell hidradenoma. AEA was seen also in tumours showing eccrine differentiation, even though it is not present in normal eccrine sweat ducts.
Jaundice Due to Cancer Of Head of the Pancreas
Authors: Phillip E. Lear
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Icterus due to malignant disease in the region of the head of the pancreas and distal common bile duct all too often heralds the presence of an incurable condition. At what stage the lesion will produce regurgitation jaundice is of clinical significance and depends for the most part on the hydrodynamics of the biliary tree. The case presented highlights this, as well as the importance of the phosphatase-bilirubin dissociation. <h3>Report of a Case:—</h3> A 57-year-old diabetic man was admitted to the hospital with a three-month history of anorexia, a 25-lb weight loss, epigastric pain, and intermittent pruritis without jaundice. A globular mass was present in the right upper quadrant. The bilirubin value was 1.5 mg/100 cc, with a direct value of 1 mg/100 cc, at the time of admission. Repeated one week later, the value was 2.25 mg/100 cc, with a direct value of 1.53 mg/100 cc.
The new UK antimicrobial resistance strategy and action plan
Authors: A. S. Kessel, M. Sharland
Journal: BMJ (2013)

A major societal, political, clinical, and research challenge 

This week the chief medical officer highlighted in her report how the rise of antimicrobial resistance (AMR) poses a threat to healthcare delivery in the United Kingdom.1 This will be followed shortly by the Department of Health’s new UK Five Year Antimicrobial Resistance Strategy and Action Plan, which will reflect the need for a clear change in the understanding and response to AMR by the public, the NHS, and the government in the UK. The rise of AMR as a serious health threat is due to the international spread of multidrug resistant (MDR) Gram negative bacteria, the global overuse of antibiotics in humans and animals, and the almost complete lack of new antibiotic development.2 All of these are now of direct concern to the NHS.

The 85% reduction in rates of meticillin resistant Staphylococcus aureus (MRSA) bloodstream infections seen in England between 2003 and 2011 has been remarkable. MRSA is now responsible for less than 2% of all bloodstream infections in England. Less remarked on has been the inexorable rise in the number of bloodstream infections attributable to Gram negative organisms (particularly Escherichia coli ), which now comprise more than half of the around 100 000 of these infections reported in England annually.3 Most large NHS hospitals now identify 50-100 times more patients with Gram negative bloodstream infections than those with MRSA, with antibiotic resistance rates of 10-20% and mortality rates of 30% reported for MDR forms.4 In England the successful introduction of conjugate pneumococcal vaccine means that the number of reported Klebsiella pneumoniae bloodstream infections …
Pain Control and the World Health Organization Analgesic Ladder
Authors: Norelle Lickiss
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Like many others, we welcome the increasingly systematic approach to therapeutic review articles. We wonder, however, whether there is need for a code of practice to govern the publication of systematic reviews. Thus, while we cannot argue with the presentation of data from eight studies in the article by Drs Jadad and Browman,<sup>1</sup>we are disturbed by the tone and content of the commentary. In our opinion, the authors have made a fundamental error in calling for a randomized controlled trial of a concept (the WHO three-step analgesic ladder). Indeed, it has already been demonstrated in Canada that it is difficult to evaluate the broader concept of palliative care.<sup>1</sup>Thus, to say that randomized controlled trials of the three-step analgesic ladder are necessary before we can say that it has improved the management of cancer pain is naive and irrelevant. In all areas of clinical
Rise in “no indicated risk” primary caesareans in the United States, 1991-2001: cross sectional analysis
Authors: Eugene Declercq, Fay Menacker, Marian MacDorman
Journal: BMJ (2004)

Currently, clinicians can search systematic reviews within the Cochrane Library, where they can find the Cochrane Database of Systematic Reviews and DARE.If they cannot find a pertinent review, or their interest is other than prevention and treatment, or if they want to conduct a comprehensive search, they can use the strategies presented here to identify systematic reviews in Medline.Quick searches or searching for systematic reviews in topic areas where many are available may be optimal with a high precision strategy or with the strategy that balanced sensitivity and precision.On the other hand, guideline developers and researchers may want to use a highly sensitive strategy.For all, our strategies are most useful when they are preprogrammed into search interfaces, such as the Clinical Queries in PubMed, ready to be combined with topic specific terms.
Absorption of Digoxin in Patients with Malabsorption Syndromes
Authors: William D. Heizer, Thomas W. Smith, Stephen E. Goldfinger
Journal: New England Journal of Medicine (1971)

Gastrointestinal absorption of digoxin was evaluated by use of a recently developed radioimmunoassay to measure serum levels. Eleven patients with malabsorption syndrome (nine with malabsorption and two with maldigestion due to pancreatic insufficiency) were compared with a control group of 10 patients who had no intestinal disease. All subjects received 0.25 mg of oral digoxin daily, and steady-state serum levels, reached after six days in all subjects, were determined. The mean steady-state serum digoxin level for the nine patients with malabsorption was significantly less than that for the control group (p less than 0.001), whereas levels for the two patients with pancreatic insufficiency were not significantly different from control values. These data indicate that digoxin is poorly and erratically absorbed by patients with malabsorption on the basis of mucosal defects or hypermotility but may be more normally absorbed by patients with pancreatic insufficiency.
PMO-202 Use of the Blatchford score to identify low-risk upper gastrointestinal bleeds
Authors: B R Disney, R Watson, A Blann, G Lip, C Tselepis, M Anderson
Journal: Gut (2012)

<h3>Introduction</h3> Acute upper gastrointestinal bleeding is a medical emergency associated with a significant health burden and risk of mortality. A significant proportion of patients are admitted to hospital unnecessarily for endoscopy following presentation with acute upper gastrointestinal bleeding. The Blatchford score can be used to identify patients with low-risk gastrointestinal bleeds suitable for discharge and outpatient endoscopy. However, some debate remains regarding what level of Blatchford score can be considered low-risk. The aim of this study was to assess the need for intervention in patients presenting with upper gastrointestinal bleeding based upon the admission Blatchford score. <h3>Methods</h3> All patients admitted with acute upper gastrointestinal bleeding to Sandwell and West Birmingham Hospitals NHS Trust from 1 January 2009 to 31 December 2009 were included in the study. <h3>Results</h3> Overall, 470 patients with acute upper gastrointestinal bleeding were admitted during the study period. Of these 67.2% were male and 32.8% female. The mean age of patients was 64.0±18.8 years. The most common diagnosis was peptic ulcer disease, which was found in 34.5% of patients. A Blatchford score of 0 accounted for 6.0% of patients (n=28) and 14.7% (n=69) had a Blatchford score ≤2. Of the patients admitted with a Blatchford score ≤2 none required intervention (transfusion, endoscopic therapy or surgery) and there were no deaths. These patients were significantly younger than patients with a Blatchford score &gt;2 (mean age 44.1±17.5 years for a Blatchford score ≤2 vs 67.4±18.8 years for a Blatchford score &gt;2). <h3>Conclusion</h3> Patients with acute upper gastrointestinal bleeding with a Blatchford score ≤2 did not require inpatient intervention and can be considered for early discharge from hospital with outpatient endoscopy. This strategy identified 14.7% of patients in our population that were unnecessarily admitted. Using a Blatchford score of ≤2 may help to significantly reduce hospital admissions. <h3>Competing interests</h3> None Declared.
P112 Therapeutic Whole Lung Lavage For Silicosis – First Application in the UK
Authors: B Prudon, R Attanoos, C Morgan, SC Stenton
Journal: Thorax (2012)

Silica is a highly fibrogenic dust and this is reflected in the low amounts of dust found in the lungs of those with fatal silicosis – approximately 3g in total. Despite a low workplace exposure limit for respirable silica, new cases of silicosis continue to be diagnosed. There is no effective pharmacological treatment. In China, whole lung lavage (WLL) has been performed for silicosis with evidence of improved dyspnoea at 6 months. To our knowledge the technique has not previously been attempted in the UK. We carried out WLL in 2 stonemasons with silicosis. Patient A presented aged 41 in 2007 with MRCP dyspnoea score 3, FVC 3.27L (60% predicted), and radiographic features of extensive silicosis (Category 3R, ILO classification). To determine if mineral could be removed from his lungs, a bronchoscopic lavage was performed using 180ml saline. The lavage fluid contained 4.8g/l of mineral. WLL was then performed with 7L saline on the right, and a month later 12L on the left. Each procedure lasted approximately 1 hour and the patient was discharged without complication within 24 hours. The washings contained 0.66g/l mineral. The total removed was approximately 7.9g, 50% of which was silica, (silica content was determined by transmission electron microscopy with energy dispersive x-ray spectrometry). On review at 6 months there had been no clinical or radiological changes. <h3>Patient</h3> B presented aged 31 with MRCP dyspnoea score 2, FVC 3.96L (65% predicted), and radiographic features of silicosis (Category C). A 9L right WLL produced considerably less mineral (0.09g/l: total approximately 0.1gm). 21% was silica. These cases demonstrate that WLL is acceptable and safe in patients with silicosis in the UK, and that substantial quantities of mineral can be removed from the lungs. It is postulated that reducing the silica burden will slow the rate of disease progression, but there is no evidence in support of that. Evidence will be difficult to adduce given the variable nature of silicosis and its relatively slow rate of progression. In the meantime, we suggest that WLL is considered for younger patients with advanced silicosis.
Reliability of endoscopy in the assessment of variceal features
Authors: Luigi Pagliaro, G. Paolo Spina, Gennaro D'Amico, Emilio Brocchi, GianCarlo Caletti, Felice Cosentino, Roberto De Franchis, Emilio Di Giulio, Giampiero Rigo, Marco Zoli, Fabio Tinè, Mariano Amuso, Claudio Antona, Luigi Buri, Giovanni Cucchiaro, Maria Di Giovanni, Fabrizio Galeotti, Giovanni Gatto, Giacomo Magnani, Diego Martines, Roberto Mazzanti, Piergiorgio Mosca, Enrico Opocher, Roberto Santambrogio, Domenico Taranto, Mario Traina, Vincenzo Ziparo
Journal: Journal of Hepatology (1987)
Physical Activity Promotion Through Primary Care
Authors: Paul A. Estabrooks, Russell E. Glasgow, David A. Dzewaltowski
Journal: JAMA (2003)

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