tbuckley/cabot-search huggingface dataset:
Effect of physical activity on epigenetic markers for breast cancer
Authors: Yvonne Coyle, David Euhus, Linda Hynan, John Minna
Journal: Cancer Research (2005)

3223  Background: Physical activity reduces breast cancer risk by 20-30%. Thus, it would be important to determine if epigenetic markers for breast cancer can be used to monitor the effectiveness of physical activity interventions for breast cancer prevention. Physical activity may lower the cumulative level of lifetime exposure to circulating estrogens as the result of absent or shorter menstrual cycles. Although the relationship between estrogen and the DNA-methylation of promoter regions of genes is unknown, there is evidence in mice that estradiol and diethylstilbestrol elicit DNA methylation changes that results in uterine tumors. Recently, it has been shown that aberrant DNA methylation of tumor suppressor genes (TSGs), RASSF1A and APC, in benign breast tissue is associated with higher breast cancer risk, measured by the Gail model. Methods: We conducted a case-control study in pre- and post-menopausal women without breast cancer to determine the effect of lifetime physical activity on the DNA methylation status of the APC and RASSF1A TSGs in benign breast tissue. Lifetime physical activity for all types (occupation, household, and exercise and sports) was obtained by an interviewer-administered questionnaire, and converted into metabolic equivalent (MET) hrs/wk. Breast cells were obtained using random periareolar fine-needle aspiration. DNA methylation status for the APC and RASSF1A TSGs in genomic DNA derived from breast cells was determined using methylation-specific PCR. Two independent samples t test analyses was performed to determine the difference between MET hrs/wk for lifetime physical activity and its different types with and without aberrant methylation for the APC and RASSF1A TSGs in breast cells. Results: Thirty-one women participated in the study. Aberrant methylation for the APC, RASSF1A, and APC + RASSF1A genes was noted in 9, 13, and 7 study subjects respectively. Lifetime physical activity was inversely associated with aberrant methylation for the APC and APC + RASSF1A genes, with P = 0.22 and P = 0.29 respectively. Lifetime physical activity for sports and exercise as a type had the highest inverse association with aberrant methylation for the APC and APC + RASSF1A genes, with P = 0.07 and P = 0.24 respectively. Also, lifetime physical activity for occupation as a type had a positive association with aberrant methylation for the APC, RASSF1A, and APC + RASSF1A genes, with P = 0.46, P = 0.21, and P = 0.37 respectively. Conclusions: The study, based on the trend in its current sample, suggests that lifetime physical activity, primarily sports and exercise, is inversely associated with aberrant methylation for the APC and RASSF1A genes individually and the APC + RASSF1A genes combined. Also, higher psychological stress levels at work may reduce the cancer protective effect of occupational physical activity, or that those with lower sports and exercise physical activity over-reported for occupational physical activity.
Soundings: Bag of bones
Authors: Liam Farrell
Journal: BMJ (2003)

Whenever a new patient joins the practice I look through the chart from back to front. When read in chronological order a chart becomes a kind of storybook, so it's less like real work (although if a chart consists of more than five volumes, I speed read).

The charts tell us as much about the changing nature of medical practice as they do about the patients. The old GP notes are terse but colourful one liners—“swinging the Pb”—and the old dog eared hospital letters are full of value judgments and sarcasm—“This patient came in on crutches; I relieved him of them and sent him on his way.”

Nowadays GP notes are rather obsessively comprehensive and hospital letters objective and cold, both perhaps lacking in nuance and a mite less informative than before. Each life unfolds in leaps and starts. Plenty of notes on childhood infections, then a big gap, interrupted for women by the pleasant meadows of fertility and childbearing.

Some people are unlucky to be struck by early illness, asthma, inflammatory bowel disease, or depression, but for most of us the chart remains thin and sketchy till we reach the 40s. Then the first pale intimations of mortality start, dim drums throbbing in the hills half heard. Minor harbingers of doom start to appear—hypertension, osteoarthritis, gratuitous counselling—and from then on the entries and reports multiply. Sickness piles on sickness, cancer piles upon degenerative disease, piles pile upon piles, like Pelion on Ossa, as this is one storybook that will not have a happy ending and with each page the grave yawns a little wider (and gives the occasional burp).

But comprehensive as they may be, the clinical notes tell us little about the real person. And why should they? It's none of our business. Thomas Hardy once referred (I am quoting Stephen King on this, and I presume he wasn't making it up) to the futility of fiction. “Compared to the dullest human being walking on the earth,” he apparently said, “the most brilliantly drawn character in any novel is but a bag of bones.” And that from the creator of the magnetic Giles Winterbourne.

This limitation is absolutely fine by me. Doctors don't need to know everything and there are some things that are best undisclosed in our bag of bones: we all have a few skeletons in our cupboard.
Outpatient Parenteral Antimicrobial-Drug Therapy
Authors: D N Gilbert, R J Dworkin, S R Raber, J E Leggett
Journal: New England Journal of Medicine (1997)

Over the past 20 years, outpatient parenteral therapy with antimicrobial drugs has proved effective, safe, and cost effective for patients with a wide range of infectious diseases.14 Teams to manage this type of therapy have been established at medical centers,5,6 emergency departments,7 health maintenance organizations,8 physicians' offices,9,10 and other sites.IndicationsThree criteria must be met before outpatient parenteral antimicrobial-drug therapy can be implemented. The patient must have an active infectious disease that requires continued treatment beyond the anticipated period of hospitalization. There should be no further need for hospitalization, other than for treatment of the infectious . . .
Non-invasive Detection of Coronary Artery Disease Using Blood Oxygen Level-dependent Magnetic Resonance Imaging at 3 Tesla
Authors: Jayanth R Arnold, Theodoros D Karamitsos, Paul Bhamra-Ariza, Jane M Francis, Nick Searle, Matthew D Robson, Paolo G Camici, Adrian P Banning, Stefan Neubauer, Michael Jerosch-Herold, Joseph B Selvanayagam
Journal: Circulation (2009)
Case 31-1996
Authors: Anthony L. Mansell, Eugene J. Mark
Journal: New England Journal of Medicine (1996)

Presentation of CaseAn 18-month-old boy was admitted to the hospital because of a persistent cough and increasing tachypnea.The infant had been born at 31 weeks' gestation. A grade 1 intraventricular hemorrhage, detected by cranial ultrasonographic examination during the neonatal period, was complicated by hyperbilirubinemia and transient apnea. Twelve months before the current admission, an evaluation performed because of lethargy and delayed development resulted in a diagnosis of intracranial neuroblastoma, without radiographic evidence of metastatic disease. The tumor was partially resected, and cycles of vincristine and cyclophosphamide were alternated with cycles of etoposide and cisplatin at three-week intervals. Nine . . .
Antacid Pharmacology in Duodenal Ulcer
Authors: John S. Fordtran, J. A. H. Collyns
Journal: New England Journal of Medicine (1966)

THE value of antacid drugs in the management of duodenal (and gastric) ulcer is controversial. Some consider antacids the keystone of medical therapy,1 others believe that they are of doubtful value,2 , 3 and some do not use them at all.4 Much of the skepticism concerning antacids, even among those who regard them as valuable, is related to their short duration of action (twenty to forty minutes), which in turn is related to the rapidity of gastric emptying. For instance, it has been estimated that a single 4-gm. dose of calcium carbonate is enough to neutralize all the gastric acid secreted by . . .
Vagal-Body Tumor (Chemodectoma of the Glomus Intravagale)
Authors: Patricio E. Perez, Edgar G. Harrison, William H. ReMine
Journal: New England Journal of Medicine (1960)

A MASS presenting in the anterolateral aspect of the neck is always a problem in clinical diagnosis. Last among the possibilities considered is chemodectoma (nonchromaffin paraganglioma) —and particularly vagal-body tumor — because of its rarity as compared with the several other kinds of tumors that may appear in the neck.A chemodectoma presenting in the neck, however, may have arisen from any of several morphologically similar nests of cells known as chemoreceptors, including the well known carotid body, the vagal body and the glomera along the cervical portion of the vagus nerve.1 , 2 In addition, a tumor of the glomus jugulare . . .
NIMG-3118F-METHYLCHOLINE PET/CT AND MAGNETIC RESONANCE SPECTROSCOPY IMAGING AND TISSUE BIOMARKERS OF CELL MEMBRANE TURNOVER IN PRIMARY BRAIN GLIOMAS - A PILOT STUDY
Authors: Matthew Grech-Sollars, Katherine Ordidge, Lesley Honeyfield, Babar Vaqas, Sameer Khan, Kevin O'Neil, David Peterson, Federico Roncaroli, David Towey, Tara Barwick, Adam Waldman
Journal: Neuro-Oncology (2015)

BACKGROUND: Choline containing compounds are key components of cell membranes; their metabolism important in membrane turnover, and therefore cellular proliferation. Choline elevation has been reported as a marker of aggressive glioma phenotype in numerous in vivo magnetic resonance spectroscopy (MRS) studies, and more recently 18F-methylcholine-PET has been applied to glioma characterisation. This preliminary study aims to examine the relationship between MRS and PET imaging choline measures in defined tumour regions, and validate these against tissue biomarkers of choline metabolism and proliferation. METHODS: A prospective pilot study of 12 subjects, aged 18-80, with suspected primary supratentorial glioma of varying grades suitable for biopsy/resection. An MRI protocol, including multivoxel MRS (TE = 30ms; TR = 1500ms), was acquired at 3T using a 32 channel head coil; PET/CT was performed with 285MBq of 18F-methylcholine with a dedicated 45 minute brain dynamic list mode acquisition. Stereotactic biopsies were obtained using neuronavigation from low and high choline areas identified on imaging, fused with high resolution structural images. RESULTS: Preliminary data from 8 patients suggests spatial concordance between high choline uptake on PET and elevated MRS choline/creatine ratios. Tissue from 4 patients (2 WHO grade-II, 2 grade-III) showed high choline areas on imaging correlate with reactive gliosis and macrophage infiltrates, but no mitotic activity or denser cellularity. In one predominantly grade II astrocytoma, areas of elevated uptake on PET showed denser cellularity and mitoses, in keeping with early malignant progression. CONCLUSIONS: Preliminary findings suggest choline PET and MRS may detect regions of inflammatory infiltrate, rather than showing a simple relationship with high tumour cellular proliferation. In one case, elevated choline uptake on PET corresponded to early focal malignant transformation. Whilst these imaging methods show continued promise for glioma characterisation, further validation against tissue enzymatic and genetic biomarkers, and clinical outcomes is essential for their rational translation into wider clinical practice.
A Large Epithelial Splenic Cyst
Authors: Shmuel Avital, Hanoch Kashtan
Journal: New England Journal of Medicine (2003)

To the Editor: Cystic lesions of the spleen are rare findings. We describe a patient with a very large epithelial splenic cyst. A 32-year-old woman presented to our clinic with a several-month history of abdominal pain and a sensation of fullness in her left upper abdomen. Physical examination revealed a large mass occupying the left and middle portions of the abdomen. Computed tomography revealed a very large splenic cyst with compression of adjacent viscera (Figure 1A). Laboratory tests revealed thrombocytopenia: 94,000 platelets per cubic millimeter. Serologic tests were negative for parasitic infection. At surgery, the spleen was mobilized (Figure 1B), . . .
PWE-255 An unresolved issue: mechanical bowel preparation for left sided colorectal surgery
Authors: A Yee, S-A Lim, RA Adair, DA Burke
Journal: Gut (2015)

<h3>Introduction</h3> This study was undertaken to assess the potential benefit of undertaking a mechanical bowel preparation when looking purely at a population of patients undergoing surgery for a left sided colorectal cancer. <h3>Method</h3> Retrospective data from October 2010 to October 2011 on left sided colorectal cancers was obtained from the colorectal cancer databases and case notes. Patients were allocated to one of 9 colorectal surgeons by chance. Each surgeon had a practice of either MBP or phosphate enema (PE) pre-operatively. Leak rate, comprising clinical and radiological leaks, and complications were measured. <h3>Results</h3> One hundred and thirty-three patients were identified. There were 23 anastomotic leaks (19 radiologically detected and 4 clinically), of which 12 received MBP and 11 no-MBP. The anastomotic leak rate (MBP group vs. no-MBP group; 30.0% vs. 11.8% p = 0.011) and 30 day morbidity (MBP group vs. no-MBP group; 50.0% vs. 32.3% p = 0.171) were higher in the MBP group. A strong association was found with MBP and at least 1 surgical site infection, 35.0% (MBP) vs. 16.1% (no-MBP) p = 0.016. As expected, surgical height of the tumour was found to be a predictor for anastomotic leak with 39.5% (below the peritoneal reflection) vs. 6.7% (above the peritoneal reflection) p = 0.001. There was no difference in 30 day mortality between the 2 groups, MBP −2.5%, no-MBP −3.2%. <h3>Conclusion</h3> The results of this study do not show any advantage with pre-operative MBP in left sided colorectal cancer surgery. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Bretagnol F, <i>et al</i>. Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial. Ann Surg. 2010;252(5):863–8 NPSA. Rapid Response Report<i>: Reducing risk of harm from oral bowel cleansing solutions</i>. 2009 13/08/2014]; Available from: http://www.npsa.nhs.uk/corporate/news/new-guidance-following-laxative-errors-in-nhs/ Contant CM, <i>et al</i>. Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial. Lancet. 2007;370(9605):2112–7 Gustafsson UO, <i>et al</i>. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS(R)) Society recommendations. Clin Nutr. 2012;31(6):783–800 Slim K, <i>et al</i>. Updated systematic review and meta-analysis of randomized clinical trials on the role of mechanical bowel preparation before colorectal surgery. Ann Surg. 2009;249(2):203–9
Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer.
Authors: Eunice Lee Kwak, Patricia LoRusso, Omid Hamid, Filip Janku, Muaiad Kittaneh, Daniel Virgil Thomas Catenacci, Emily Chan, Tanios S. Bekaii-Saab, Benny Amore, Yuying C. Hwang, Rui Tang, Gataree Ngarmchamnanrith, David S. Hong
Journal: Journal of Clinical Oncology (2015)

1 Background: Dysregulation of the MET pathway can promote tumor growth and metastasis. AMG 337 is an investigational, oral MET kinase inhibitor that is being evaluated in a first-in-human study. Here we describe the clinical activity, safety, and tolerability of AMG 337 in ptswith MET-amplified GEJ, G, and E cancers. Methods: Key eligibility criteria: age ≥ 18 years, advanced solid tumors, measurable disease, ECOG ≤ 2, adequate organ function. AMG 337 was administered QD or BID. Starting dose was 25 mg, with planned dose escalation of 50–500 mg QD and 100–200 mg BID. Ptswith MET overexpression/amplification/mutation could enroll to the highest dose deemed safe at any time. Results: As of April 2014, 80 pts had received ≥ 1 dose of AMG 337. Median (range) age, 58 (19–79) years; men, 61%; ECOG ≤ 1, 96%. Of the 51 pts with pre- and post-central read data, 10 pts had MET-amplified GI cancers (all of which were GEJ, G, or E cancers). Responses in these pts are shown in the table. One pt had a complete response (duration 100 wks) and 4 pts had partial responses (durations up to 52 wks). The most common treatment-emergent AEs (in &gt; 20% of all pts) were headache, nausea, fatigue, vomiting, and constipation. AEs and dose-limiting toxicities were reported previously (Hong et al., ASCO 2014). The AE profile of pts with GI cancers was comparable to that of all ptsenrolled in the study. QD maximum tolerated dose (MTD) is 300 mg; BID MTD has not been reached. Conclusions: Responses to AMG 337 were observed in a subset of pts with MET-amplified GI tumors. A dose-expansion phase will enroll up to 50 ptswith MET-amplified tumors at the MTD. Clinical trial information: NCT01253707. [Table: see text]
Abstract 3084: Accuracy of Multidetector CT in Assessing the Degree of Stenosis Caused by Calcified Coronary Artery Plaques
Authors: Shaoxiong Zhang, David Levin, Ethan Halpern, David Fischman, Michael Savage, Paul Walinsky
Journal: Circulation (2007)

Purpose: Because of beam hardening and blooming artifacts, it is difficult to determine the degree of stenosis caused by calcified CAPs at CCTA. Our goal was to determine how accurate CCTA is in evaluating these lesions. Method &amp; Materials: Thirty-one patients who had 1 or more calcified CAPs at CCTA underwent cardiac catheterization (cath). CCTAs were reviewed by 2 experienced radiologists blinded as to cath results. CCTAs were performed on 40- and 64-detector row CTs (Philips Medical Systems, Cleveland, OH) and post-processed using Philips Brilliance workstations. The size of the calcified CAPs was graded subjectively as small, moderate, or large. Using post-processing techniques such as segmentation and tracking, we attempted to determine whether the calcified lesions were obstructive (&gt;50% diameter narrowing) or nonobstructive (&lt;50% diameter narrowing). Concordance with cath was then determined. Results: Calcified CAPS were graded as small at 61 locations, moderate at 22 locations, and large at 43 locations. With small calcified CAPs, CCTA and cath were concordant in 58/61 (95%). CCTA overestimated the degree of stenosis in 2 and underestimated it in 1. With moderate-sized calcified CAPs, CCTA and cath were concordant in 20/22 (91%). CCTA overestimated the degree of stenosis in the other 2. With large calcified CAPs, CCTA and cath were concordant in 29/43 (67%). In all the other 14, CCTA overestimated the degree of stenosis. In detecting obstructive lesions caused by the large calcified CAPs, CCTA sens=100%, spec=44%, PPV=56%, NPV=100%, accuracy=67%. Conclusion: CCTA accurately predicts the presence of obstructive disease in &gt;90% of small and moderate-sized calcified CAPs. With large calcified CAPs, CTA correctly predicts presence of obstructive disease about 2/3 of the time. When errors occur, they are virtually always due to overestimation of the degree of stenosis.
M2 Using a Transportable Oxygen Concentrator (TPOC) to facilitate prompt and safe hospital discharge
Authors: F Hamilton, G Luxford, J Bott
Journal: Thorax (2015)

<h3>Introduction</h3> Whilst current guidelines<sup>1</sup> state that patients must be clinically stable prior to commencing home oxygen, respiratory patients can be discharged with a supply of oxygen. Multiple errors are often found on the Home Oxygen Order Forms (HOOFs) for hospital discharges and equipment requirements are often subsequently changed, generating wasteful activity and costs. The aim was to establish whether a TPOC could be provided to specialist respiratory teams within hospitals to promote efficient and safe discharge for those patients requiring home oxygen. <h3>Method</h3> Three hospitals with established Home Oxygen Assessment and Review Services (HOSAR) were issued with TPOCs. The Home Oxygen Supplier trained the HOSAR clinicians on use, and supplied written documentation on safety. The clinicians identified appropriate patients based on clinical assessments and issued them with a TPOC. A HOOF was then sent to the supplier with appropriate equipment for the patient’s long term needs. On installation of this, the supplier removed the TPOC and another was issued to the hospital to enable an ongoing supply. <h3>Results</h3> Of those discharged with a TPOC and a subsequent HOOF, only 5% (n = 6) of patients required a modality change or HOOF update within the following month, compared to 40% (n = 33296) of all other HOOFs received (Figure 1). The largest group of patients issued with a TPOC on discharge were clinically coded as COPD (40%), followed by those coded as Palliative Care (28%). <h3>Conclusion</h3> The results demonstrate the practical uses of a TPOC for hospital discharge in clinically appropriate patients and a greater degree of control over the accuracy of ordering. A precise cost saving cannot be demonstrated as it is unclear how many bed days were saved, but it is clear that a reduction in wasteful activity by more accurate ordering would have reduced costs. <h3>Discussion</h3> By using staff trained on equipment and accurately completing HOOFs, combined with equipment readily available, transition from hospital to home can be both clinically accurate, time efficient and cost effective. <h3>Reference</h3> 1 Hardinge M, Annandale J, Bourne S, <i>et al</i>. British Thoracic Society guidelines for home oxygen use in adults. <i>Thorax</i> 2015;<b>70</b>:i1–i43
184P: The efficacy and safety of amrubicin in non-small-cell lung cancer patients beyond third-line therapy
Authors: M. Saigusa, S. Sakurai, T. Akamatsu, A. Yamamoto, Y. Shishido, T. Akita, S. Morita, K. Asada, T. Shirai, T. Eto
Journal: Journal of Thoracic Oncology (2016)