tbuckley/cabot-search huggingface dataset:
The Stereoselective Interaction of Warfarin and Metronidazole in Man
Authors: Robert A. O'Reilly
Journal: New England Journal of Medicine (1976)

Because of the known interaction of warfarin and disulfiram and the "disulfiram effect" of metronidazole, the interaction with metronidazole of commercial racemic warfarin and its separated enantiomorphs was evaluated in eight normal subjects. Single oral doses of racemate, S(-)-warfarin, and R (+)-warfarin, were administered in the amounts of 1.5, 0.75 and 1.5 mg per kilogram of body weight, respectively, with and without metronidazole, 750 mg by mouth, beginning seven days before the warfarin dose and continuing seven days before the warfarin dose and continuing daily throughout the hypoprothrombinemia. Daily plasma samples were analyzed for warfarin in content and one-stage prothrombin time. A highly significant (P less than 0.01) augmentation of the mean warfarin level and hypoprothrombinemia with metronidazole occurred for racemic and S (-)-warfarin; none occurred with R (+)-warfarin. Thus, the interaction of racemic warfarin and metronidazole is stereoselective and can be lessened or even avoided by use of R (+)-warfarin alone for long-term therapy.
CHADS-VASC SCORE AND THE RISK OF NEW ONSET ATRIAL FIBRILLATION AMONG MIDDLE AGE ADULTS
Authors: Anat Berkovitch, Avi Sabbag, Shlomo Segev, Shaye Kivity, Yechezkel Sidi, Ilan Goldenberg, Elad Maor
Journal: Journal of the American College of Cardiology (2016)
Abstract 2187: Optimization free oncogene mutation screening work flow
Authors: Jonathan T. Wang, Michael K. Lee, Gordon A. Janaway, Nathalie Koch, Elke Geuns, Junko F. Stevens
Journal: Cancer Research (2010)

Abstract BRCA1 and BRCA2 are the two primary breast cancer susceptibility genes in which identifying mutations is important to access cancer risk and decision for treatment. Prescreening of exons by High Resolution Melt (HRM) prior to sequencing can reduce effort in mutation screening in large transcripts such as the BRCA genes. Published methods for BRCA1 and 2 HRM screening have relied on complicated touchdown cycling protocols and custom reagent mixes that can lead to variable result. We have validated a streamlined workflow for adaptability in a clinical diagnostic environment. First, genomic DNA template was extracted on an automated sample processor using magnetic bead technology to purify genomic DNA directly from blood sample. Then, the PCR was performed using a PCR master mix optimized for HRM coupled with universal cycling conditions. We have successfully amplified all 120 amplicons covering exons of both BRCA genes using universal PCR condition. Potential variations identified by HRM screening were confirmed by direct sequencing of HRM PCR amplicons with M13 universal tags. By using unified protocol for PCR and universal sequencing for all amplicons the risk of incorrect procedure is greatly reduced. This simplified workflow for oncogene mutation screening using automated sample extraction and universal protocol for PCR and sequencing provides significant advantages for application in diagnostic settings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2187.
IDENTIFYING STABLE CHEST PAIN PATIENTS WITH SUSPECTED CORONARY DISEASE IN WHOM NONINVASIVE TESTING MAY BE SAFELY DEFERRED: INSIGHTS FROM THE PROMISE TRIAL (PROSPECTIVE MULTICENTER IMAGING STUDY FOR EVALUATION OF CHEST PAIN)
Authors: Christopher B. Fordyce, Pamela S. Douglas, Rhonda S. Roberts, Manesh R. Patel, Udo Hoffmann, Daniel B. Mark, Hussein Al-Khalidi, John Kostis, Kerry L. Lee, James E. Udelson
Journal: Journal of the American College of Cardiology (2016)
Dose-Ranging Trial of Zacopride: The Emetic Antiemetic?
Authors: K. M. W. Pisters, M. G. Kris, L. B. Tyson, R. A. Clark, R. J. Gralla
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Dose-Ranging Trial of Zacopride: The Emetic Antiemetic? Get access Katherine M. W. Pisters, Katherine M. W. Pisters * Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical CollegeNew York, N.Y. *Correspondence to: Katherine M. W. Pisters, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark G. Kris, Mark G. Kris Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical CollegeNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leslie B. Tyson, Leslie B. Tyson Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical CollegeNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rebecca A. Clark, Rebecca A. Clark Present address:Oschner Cancer InstituteNew Orleans, La. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard J. Gralla Richard J. Gralla Present address:Oschner Cancer InstituteNew Orleans, La. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 9, 6 May 1992, Pages 717–718, https://doi.org/10.1093/jnci/84.9.717 Published: 06 May 1992 Article history Received: 23 September 1991 Revision received: 24 February 1992 Accepted: 02 March 1992 Published: 06 May 1992
Theatre: Jackson Ward
Authors: T. Delamothe
Journal: BMJ (2001)

Jackson Ward. By James Scott. Old Red Lion, 418 St John Street, London EC1, until 28 April (no performance Monday 23 April)

It's Dr Jack Jackson's last week as senior consultant at a rural district general hospital. There's the hospital concert in his honour to endure—replete with execrable sketches—and the opening of a new ward that bears his name. Speeches, buns, and tea from a big urn. “What would it have been like if you'd been really famous,” wonders his wife.

But none of it makes much of an impression on Dr Jackson. Indigestion was the only thing that had really mattered in his world; everything else seemed insubstantial by comparison. “It's as if a dark haze had settled over me,” he says soon after his retirement, and it doesn't lift.

It turns out that absorption in his work had left him no time for children, hobbies, or close friendships. He plays golf with a widowed colleague who retired a few years before him, but although he drops in for dinner twice a week he hardly knows him. He tries touring with his wife and golfing partner, but Scotland “all looks the same,” and they return early.

He and his wife see the obvious solution as a return to his old hospital in some capacity or other. Couldn't they spare him a few of his old patients to see? But it's not on. His replacement as senior consultant blocks an attempt for him to be awarded emeritus status. And he reminds him to return his parking permit. The only person who offers anything like empathy is a professional patient who seems to haunt the outpatient department. Her remedy for the vicissitudes of life—retirement included—is an operation.

Meanwhile, Jackson tries to recall a forgotten statistic: within 18 months of retirement, one third of doctors have a heart attack, one third have a psychiatric breakdown, but what happens to the other third? Presumably, what's happening to him.

Jackson engineers his admission to his old hospital, “with some sort of failure—heart, liver, kidney . . . brain.” The admitting doctor doesn't quibble.

It used to be for death that one had to get one's affairs in order. This play suggests that retirement deserves at least as much preparation and that overimmersion in work is not a good start. Doctors of all ages might take note.

Jackson Ward began life as a radio play (BMJ 1990; 301:993), and it must have made bleak listening. But this production is played for wry laughs; the professional patient could guy an entire comedy series. Playwright James Scott insists it's a “gentle play about retirement.” Scott, whose fifth play this is, is consultant orthopaedic surgeon at Chelsea and Westminster Hospital and chairman of its arts projects. He retires in August.
Relief of Spinal Cord Compression from Vertebral Hemangioma by Intralesional Injection of Absolute Ethanol
Authors: John D. Heiss, John L. Doppman, Edward H. Oldfield
Journal: New England Journal of Medicine (1994)

Vertebral hemangiomas are relatively common abnormalities. They have been found in 10.7 percent of spines at autopsy and in 14.2 percent of people over the age of 60 years1. However, neurologic symptoms, which result from epidural compression of the spinal cord by the hemangioma, hypertrophied bone, epidural hemorrhage, or compression fracture, are uncommon2,3. Current treatments for symptomatic vertebral hemangioma include surgery, radiotherapy, and transarterial embolization4. Surgical treatment is often associated with profuse hemorrhage, incomplete resection, and lengthy convalescence5–7. Although radiotherapy is moderately effective, its effects on the hemangioma are delayed, and there is a . . .
Coarctation of the Aorta Demonstrated by a Radionuclide First-Pass Flow Study Using Tc-99m Tetrofosmin
Authors: Ariwan Rakvit, Gary Meyerrose, Leigh A Jenkins, Jennifer Harris, Ramiro Sanchez, S Lane Cox, Juan Kurdi, Adam Gunder
Journal: Clinical Nuclear Medicine (2002)

RAKVIT, ARIWAN M.D.*; MEYERROSE, GARY M.D.†‡; JENKINS, LEIGH A. M.D.†; HARRIS, JENNIFER R.T.N., C.M.M.T.‡; SANCHEZ, RAMIRO R.T.R., C.M.M.T.‡; LANE COX, S. M.D.†; KURDI, JUAN M.D.†; GUNDER, ADAM M.D.* Author Information
Tory MP attacks government for “entirely unreasonable” tactics in junior doctors’ dispute
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Sarah Wollaston, the Conservative MP for Totnes and a former GP, has criticised the government for employing “entirely unreasonable” tactics and misrepresenting evidence about seven day working during the ongoing dispute with junior doctors.

Wollaston, who now leads the House of Commons health select committee, also said that the Department of Health should have been firmer in stating to the prime minister that seven day routine services in the NHS will be “unachievable” with the current workforce and financial pressures.

Writing in the Guardian newspaper,1 Wollaston dismissed claims from England’s health secretary, Jeremy Hunt, that increasing the number of doctors working at weekends would reduce hospital deaths.

Her intervention exposed the depth of disagreement in the Conservative Party about …
Abstract P4-05-05: Stromal Response to 14-Day Preoperative Therapy in Postmenopausal Oestrogen Receptor Positive Breast Cancer
Authors: C Lo, S Busch, AG Lee, G Searle, R Lamb, A Cramer, MC Winter, RE Coleman, M Dixon, NJ Bundred, G. Landberg
Journal: Cancer Research (2010)

Abstract Background: Stromal-epithelial interaction is a key factor in tumour progression. Cancer-associated fibroblasts (CAFs) and macrophage infiltration have been associated with early relapse in breast cancer. Bisphosphonates are effective inhibitors of osteoclast activation in metastatic breast cancer but also have a general inhibitory effect on breast cancer progression. In order to monitor a potential tumour stromal response in breast cancer during treatment with an aromatase inhibitor and a bisphosphonate we analysed pre-and post-treatment samples from a neoadjuvant window study and focused on the presence of macrophages and CAFs. Materials and methods: Tissue microarrays (TMAs) from surgical samples and pre-operative core biopsies were immunohistochemically stained for aSMA (CAF marker), CD68 (macrophages) and epithelial proliferation (Ki67). In order to validate if the presence of macrophages and aSMA could be monitored by the TMA approach, we initially analysed a screening cohort of 144 breast cancer samples. We then studied pre-and post-treatment samples from 110 postmenopausal ER-positive invasive breast cancer patients randomised to receive 14 days of preoperative treatment (placebo, Letrozole, or Letrozole plus Zoledronate). Results: In the screening cohort, we observed significant links between aSMA positive fibroblasts and disease recurrence as well as between CD68 positive macrophages and tumour size, grade, lymph node positivity and recurrence. This validated the use of TMAs for stromal analyses and furthersupported a link with key tumour biological events. In both treatment arms, there was a significant drop in absolute Ki67 value compared to placebo (-9.3% Letrozole and -13.1% combination reduction versus 1% increase, P&amp;lt;0.001). Post-treatment CD68 (median 35, range 3 to 117) was significantly linked to a Ki67 drop (p=0.045). Interestingly, this effect was mainly observed in the combination treatment group (p=0.002). aSMA expression was unaffected during treatment in 52%, increased in 35% and decreased in 13% of cases. Patients with aSMA reduction post treatment had a larger Ki67 fall compared to patients with increase or no change in aSMA (p=0.007). Conclusion: Short term treatment response in the epithelial component of cancers was paralleled by specific responses in the tumour stromal component. These novel findings suggest that bisphosphonates and aromatase inhibitors have major effects on tumour stroma in vivo which might augment their inhibitory effect on tumour progression. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-05-05.
EVALUATION OF RIGHT ATRIAL FUNCTION AND PROGNOSIS USING SPECKLE-TRACKING IMAGING IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION
Authors: Konomi Sakata, Yoichiro Uesugi, Aoi Isaka, Toshinori Minamishima, Kenichi Matsushita, Toru Satoh, Hideaki Yoshino
Journal: Journal of the American College of Cardiology (2015)
CULPRIT VERSUS MULTI-VESSEL PERCUTANEOUS INTERVENTION IN ST ELEVATION MYOCARDIAL INFARCTION PATIENTS WITH CARDIOGENIC SHOCK: META-ANALYSIS
Authors: Arun Kanmanthareddy, Scott Lilly, Venkata Alla, Michael White, Abilash Balmuri, Claire Hunter, Manu Kaushik, Dennis Esterbrooks, Aryan Mooss, Michael Del Core
Journal: Journal of the American College of Cardiology (2016)
Abstract ES3-2: Challenges to Clinical Application of New Discoveries in the Genetics of Breast Cancer Predisposition
Authors: ME Robson
Journal: Cancer Research (2010)

Abstract In the United States, testing for mutations in BRCA1 and BRCA2 has become a routine part of the management of individuals at risk for hereditary breast and ovarian cancer. Most providers accept the clinical utility of such testing. This acceptance rests upon a consensus that clinical management of mutation carriers should differ from that of non-carriers. The factors that justify differential management are: 1) the strength of the predisposition, 2) the strong association between mutation and risk in an individual, which allows presymptomatic testing, 3) the risks for component tumors that may not be evident from the family history, and 4) the availability of interventions that are perceived to be effective, even if the evidence base demonstrating such effectiveness is less than robust. Evolving evidence that affected mutation carriers may benefit from specific local or systemic treatment approaches further increases acceptance. Only a small number of breast cancer patients carry BRCA1 and BRCA2 mutations. A few more women carry other high penetrance alleles, but the clinical utility of testing for some of these (e.g. TP53) is less clear than for BRCA1/2, which illustrates that the strength of a predisposition is not the only determinant of clinical utility. High penetrance alleles only account for a small fraction of the hereditable risk of breast cancer. Several groups have described a number of rare variants of lesser risk (RR approximately 2), such as ATM, CHEK2, BRIP1, and PALB2). Large genome-wide association studies have identified additional common variants with even lower relative risks. The identification of these rare and common risk variants may provide important insights into breast cancer biology, but the clinical utility of testing is limited at the present time. We will discuss possible approaches to incorporating information about these risk variants into clinical practice. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES3-2.
981 IGA ANTIBODIES AGAINST DEAMIDATED GLIADIN PEPTIDES AND TISSUE-TRANSGLUTAMINASE IN PATIENTS WITH CHRONIC LIVER DISEASES
Authors: N.K. Gatselis, K. Zachou, G.L. Norman, G. Tzelas, S. Gabeta, M. Speletas, G.K. Koukoulis, G.N. Dalekos
Journal: Journal of Hepatology (2012)
Only 12 of 211 commissioning groups are acting on integrated care, conference hears
Authors: N. Hawkes
Journal: BMJ (2014)

After a decade of talk, integrated care is beginning to be commissioned in the NHS in England by the braver elements among the clinical commissioning groups (CCGs), a meeting at the King’s Fund heard on 27 March. But Bob Ricketts, director of commissioning support strategy and market development at NHS England, questioned whether it was happening fast enough to have any impact on the many problems the NHS faces.

Ricketts said the transformational change he believed necessary would have been easier “when we were flusher.” But, he added, “We are where we are and the longer we delay the greater the risk will become.” The NHS faced an unprecedented set of challenges that could only be met by changing …
THU0513 Impaired Recognition of Porphyromonas Gingivalis in Rheumatoid Arthritis Patients
Authors: K. Santegoets, M. Wenink, F. Braga, M. Cossu, F. Lamers-Karnebeek, P. van Riel, P. Sturm, W. van den Berg, T. Radstake
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and the severity of periodontitis can affect the level of arthritis. <i>Porphyromonas gingivalis</i> is one of the main bacteria involved in periodontitis and DNA from this bacterium can be found in RA synovial tissue. Furthermore, <i>P. gingivalis</i> is the only known bacterium that can citrullinate proteins, the target of autoantibodies in many RA patients. Therefore, <i>P. gingivalis</i> is a prime candidate for investigation in RA pathogenesis. <h3>Objectives</h3> Our aim was to determine possible differences in the innate immune response against <i>P. gingivalis</i> between healthy controls and RA patients. <h3>Methods</h3> Monocyte-derived dendritic cells (DCs) from healthy controls, RA and psoriatic arthritis (PsA) patients were stimulated with <i>P. gingivalis</i>, a range of other bacteria and TLR agonists. Cytokine production was determined using a Luminex-based assay and blocking studies were performed to determine which receptors were involved in differential recognition of <i>P. gingivalis</i>. Cytokine production was also determined in peripheral blood mononuclear cell (PBMC) cultures stimulated with <i>P. gingivalis</i>. <h3>Results</h3> RA DCs produced markedly less TNFα, IL-12p70 and IL-8 as compared to healthy controls upon stimulation with <i>P. gingivalis</i>, but not with the other bacteria tested. In sharp contrast, DCs from PsA patients did not differ from healthy controls, suggesting a RA-specific deregulated response to <i>P. gingivalis</i>. Cytokine production upon <i>P. gingivalis</i> stimulation did not correlate with clinical disease characteristics. The difference between RA patients and controls was abolished when complement receptor 3 was blocked. In PBMC cultures, interferon gamma induction by <i>P. gingivalis</i> was also significantly reduced in RA patients. <h3>Conclusions</h3> Immune cells from RA patients display a marked diminished response to <i>P. gingivalis</i>. This could result in prolonged survival of <i>P. gingivalis</i> and an increased oral bacterial burden in RA patients, possibly driving autoantibody formation and the characteristic self-perpetuating loop of chronic inflammation. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3229
P129p90 Ribosomal S6 Kinase contributes to NHE1 induced cardiomyocyte hypertrophy
Authors: MY Jaballah, BF Elmarayat, FS Alsulaiti, F Mraiche
Journal: Cardiovascular Research (2014)

Background: Pharmacological studies have shown that increasing the activity of Na+/H+ exchanger isoform 1 (NHE1) plays a critical role in the development of cardiac hypertrophy. Despite the importance of NHE1, direct inhibition of NHE1 has demonstrated several adverse side effects. It is has been demonstrated that p90 ribosomal S6 kinase (RSK) regulates the activity of NHE1. RSK, a downstream regulator of the mitogen activated pathway, has also been implicated in cardiac hypertrophy both in in vitro and in vivo models. The interplay between NHE1 and RSK in NHE1 induced cardiomyocyte hypertrophy remains unknown.
Endoscopic full-thickness resection based on the novel Dortmund technique
Authors: Martin Faehndrich, Michael Heike, Marcel Sandmann
Journal: Endoscopy (2014)

In 2010, we performed full-thickness resection (FTR) using the over-the-scope clip (OTSC) system (Ovesco Endoscopy GmbH, Tübingen, Germany) [1]. The key aspects of this technique are to apply the clip to the target lesion and then to resect above the ensnared lesion. However, these maneuvers require several separate accessories. Therefore, a new device to perform FTR was developed. Herein we describe the steps to perform FTR using this novel platform.
Out-of-Hospital Cardiac Arrest
Authors: Jeremy N. Ruskin, John P. DiMarco, Hasan Garan
Journal: New England Journal of Medicine (1980)

We performed electrophysiologic studies in 31 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction. At the time of resuscitation, eight patients had sustained ventricular tachycardia and 23 patients had ventricular fibrillation. Programmed right ventricular stimulation later revealed electrically inducible ventricular arrhythmias in 25 of the 31 patients (81 per cent). Complete suppression of electrically inducible ventricular arrhythmias was achieved with antiarrhythmic therapy in 19 of these 25 patients. None of the 19 patients in whom the inducible arrhythmia was suppressed before discharge has died suddenly or had a symptomatic arrhythmia after a mean follow-up of 15 months (range, five to 26 months). Of the six patients in whom inducible arrhythmias could not be suppressed, three died suddenly (one in the hospital) within six months. We conclude that ventricular arrhythmias can be initiated and reproduced by programmed ventricular stimulation in a majority of patients who have been resuscitated after out-of-hospital cardiac arrest and that complete suppression of these arrhythmias with antiarrhythmic therapy is highly predictive of survival for at least one year. (N Engl J Med. 1980; 303:607–13.)
C-11 Methionine and F-18 FDG Uptake in a Patient With Meningioma and Glioblastoma Multiforme
Authors: Meliha Korkmaz, Edmund Kim, Franklin C. Wong, Donald A. Podoloff
Journal: Clinical Nuclear Medicine (1996)

PET imaging with C-11 methionine and F-18 FDG were performed on a 75-year-old man with recurrence of a glioblastoma in the left parietal region. Markedly increased methionine and slightly increased F-18 FDG uptake were seen in another lesion in the right parietal region which was a meningioma.