tbuckley/cabot-search huggingface dataset:
BRCA1 Patent Dispute Resolved; NIEHS Included
Authors: Susan Jenks
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article BRCA1 Patent Dispute Resolved; NIEHS Included Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 412–413, https://doi.org/10.1093/jnci/87.6.412 Published: 15 March 1995
Adenine Arabinoside Therapy of Biopsy-Proved Herpes Simplex Encephalitis
Authors: Richard J. Whitley, Seng-jaw Soong, Raphael Dolin, George J. Galasso, Lawrence T. Ch'ien, Charles A. Alford
Journal: New England Journal of Medicine (1977)

Original Article from The New England Journal of Medicine — Adenine Arabinoside Therapy of Biopsy-Proved Herpes Simplex Encephalitis — National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study
Does addition of cystic fluid analysis by EUS-guided FNA to EUS image help the physician to select accurately patients with unilocular or macrocystic pancreatic cystic lesions for surgery?
Authors: LS Soo, SH Kwon, TY Lee, HC Oh, DW Seo, SK Lee, MH Kim
Journal: Endoscopy (2006)

Background and Aim: Differential diagnosis for pancreatic cystic lesions by EUS imaging remains difficult because of morphologic overlaps among them. The aim of this study was to evaluate whether additional cystic fluid analysis (CFA) obtained by EUS-guided FNA (EUS-FNA) to EUS imaging can help physician to select accurately patients with pancreatic cystic lesions for surgery. Patients and Methods: From September 2003 to May 2005, 47 consecutive patients with pathologic confirmed pancreatic cystic lesions (mucinous cystic tumor: 14, oligocystic serous cystic tumor: 10, IPMT-Branch duct type: 12, pseudocyst: 11) were prospectively studied. The endosonographers described their diagnostic confidence level (based on visual analogue scale) on the result form. We divided the enrolled cases into two groups. Confidence group was defined as those with more than 75% of confidence level and tentative group with less than 75%. Cystic fluid obtained by EUS-FNA was used for biochemical and tumor markers analysis. EUS imaging diagnosis and CFA by EUS-FNA diagnosis were compared with the final histological diagnosis obtained at surgery. Results: 26 patients were diagnosed by endosonographers with confidence on EUS image. The diagnostic accuracy was 76.9% (20/26) and 21 patients were tentatively diagnosed and the diagnostic accuracy was 61.9% (13/21). Cut-off values of CEA and CA72–4 for differentiating between premalignant and benign cystic lesion were 12.6ng/ml and 3.75 U/ml, respectively. In confidence group, the diagnostic accuracy increased to 88.5% (23/26) and, in tentative group, increased to 76.2% (16/21) which was statistically significant (p<0.05). Conclusion: Addition of CFA to EUS image may be a valuable tool in the preoperative diagnostic assessment of pancreatic cystic lesions and help the physician to select patients with cystic tumors whom to refer for surgery.
Abstract 4437: Subsquamous extension of Barrett epithelium is a regular event
Authors: Andreas H. Marx, Thomas Rösch, Guido Sauter
Journal: Cancer Research (2012)

Abstract Endoscopic resection and/or ablation of Barrett esophagus (BE) is directed by the endoscopic visual impression of pinkish Barrett versus whitish esophageal mucosa; microscopically however, BE may extend underneath squamous epithelium. Aim of the present study is to evaluate subsquamous BE extension in a large cohort of patients with endoscopically resected neoplastic BE. Resection specimens of 97 patients treated by endoscopic mucosal resection (EMR) for suspected or confirmed neoplastic BE (83 men, 14 women, mean age 65 years) were retrospective reanalyzed by two experienced GI histopathologists. Orientation of resected specimens pinned on cork was done prior to histopathological workup with squamous epithelium oriented proximally. Subsquamous extension was measured in all specimens containing squamous epithelium. Endoscopic and other histopathologic data were also analyzed. 442 specimens of the 97 study cases were analyzed and subsquamous BE was found in 42.5% of specimens or 97.9% of patients. Mean length of subsquamous BE extension was 3.5 mm (0.0-9.6 mm) with 27.8% of cases measuring 5 mm or more. In 56 cases (57.7%), subsquamous BE consisted entirely or partially of neoplasia (42 cancers, 12 HGIN, 2 LGIN) with a mean subsquamous tumor extension of 1.2 mm mm (range 0.0-5.2 mm). Subsquamous extension of BE including all forms of neoplasia is a regular event. A minimal safety margin of 1 cm has to be kept with Barrett ablation techniques in order to avoid BE and/or tumor recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4437. doi:1538-7445.AM2012-4437
THREE-DIMENSIONAL ECHOCARDIOGRAPHIC EVALUATION OF VENTRICULAR SEPTAL CIRCUMFERENTIAL STRAIN IN THE PRESENCE OF INTERVENTRICULAR DYSSYNCHRONY
Authors: David Sahn, Jason Anderson, Cole Streiff, Lydia Tam, Hannah Tam, Hao Chuan Lei, Muhammad Ashraf, Meihua Zhu
Journal: Journal of the American College of Cardiology (2015)
Soundings: Betrayal in blue pinstripe?
Authors: Kevin Barraclough
Journal: BMJ (2001)

Not long after Labour's first landslide victory, I attended a lecture by someone from the Department of Health. It was a rather odd experience. The DoH apparatchik had the appearance one would expect from superimposing all the features of an identikit box: a sort of homogenised Warren Beatty. His prose had the same sort of rather amorphous allure. Both speaker and speech would not have looked out of place in the colour supplements, between an in depth profile of Liz Hurley and a full page advertisement for Haagen-Dazs ice cream. And yet after I had listened to the speech I felt oddly better, in the same way one does after listening to Alastair Cooke on the radio: a wiser person, a confidante. It took some years for the sense of betrayal to be complete.

Last week I sat opposite another apparatchik as he explained that, because our list size was 90 patients short of the required number, we could not have a full replacement for a retiring partner. I tried to explain that we are a small, rural, non-dispensing, low earning practice. I said that we offered an extremely high level of personal care, and that we performed many procedures that would normally be carried out in hospitals. But this was of no interest to him. We were 90 patients short, and that was that.

I returned home, shaking and sweaty. On the kitchen table were piled recent missives from the DoH. They spoke of the need for more doctors, of more support for primary care, of the need for excellence and personal care. The gulf between the vacuous words before me and the unblinking indifference of the bureaucrat was breathtaking.

It was my first brush with the field of medical politics, and I felt stunned and impotent. There was about the experience a surreal passivity I normally associate with dreams: when events implode on you randomly and your fate, like that of Ulysses, is contingent on the petty jealousies of flawed gods.

Richard Smith asked a few weeks ago why doctors were so unhappy. Maybe it is because so much of what we do because we genuinely believe in the NHS is unacknowledged. Maybe it is because we seem to be powerless in the face of autocrats who do not like doctors.

But are we downhearted? Well, yes we are a little, actually.
P4 Establishing A Role For Trpv1 On Sensory Nerves In Copd Associated Chronic Cough
Authors: M. Wortley, S. Maher, S. Bonvini, E. Dubuis, J. Nasra, K. Holt, R. Dockry, S. Sen, D. Singh, J. Smith, P. Round, S. Gilbert, V. Marchant, J. Ford, M. Birrell, M. Belvisi
Journal: Thorax (2014)

<h3>Background</h3> An increase in cough reflex sensitivity to capsaicin in COPD has been described in some studies, suggesting a role for TRPV1 in the disease phenotype. We utilised a guinea-pig cigarette-smoke (CS) exposure COPD model to investigate an enhanced cough phenotype, and evaluate the role of TRPV1 using a novel clinical-ready inhibitor, XEN-D0501.<sup>1</sup> Furthermore, we confirmed enhanced cough responses in COPD patients using a dose-response capsaicin challenge to determine E<sub>Max</sub>. <h3>Methods</h3> Guinea-pigs were exposed to air/cigarette smoke (CS) for 1 h, twice daily, for 8 days. Coughs evoked by aerosolised capsaicin (30 μM), depolarisation of isolated vagus nerve tissue induced by capsaicin (1 μM), or increases in intracellular calcium [Ca<sup>2+</sup>]<sub>i</sub> to capsaicin (1 μM) in airway-terminating (i.n. DiI stained) jugular and nodose neurons were evaluated. Vagus nerve was obtained from human non-smoker/smoker subjects for similar assessment. Coughs evoked by capsaicin (4 inhalations, 0.49–1000 µM) were recorded in COPD and compared with healthy controls. <h3>Results</h3> Capsaicin-evoked cough was increased in COPD patients (Fig.1A) and in CS-exposed guinea-pigs (Fig.1B) compared to controls. Capsaicin induced greater depolarisation in nerve tissue from CS-exposed guinea-pigs, and in human vagus nerves from smokers, compared to controls. Capsaicin also induced greater [Ca<sup>2+</sup>]<sub>i</sub> increases in airway-terminating jugular and nodose (which are normally capsaicin-unresponsive) neurons from CS-exposed guinea-pigs. XEN-D0501 (i.p. 1 h before cough recording) almost completely inhibited the cough response to capsaicin in both air- and CS-exposed guinea-pigs (Fig.1B). <h3>Conclusions</h3> CS-exposure evoked increased cough to capsaicin in guinea-pigs, mimicking the enhanced cough phenotype observed in COPD patients. This was paralleled by enhanced capsaicin responses in isolated vagus nerves and airway neurons from CS-exposed guinea-pigs and in human vagus from smokers suggesting the enhanced cough phenotype is due to increased TRPV1-mediated sensory nerve responsiveness. Inhibition of the CS-enhanced cough response by XEN-D0501 further implicated a role for TRPV1. This data, together with the finding that TRPV1 KO mice display less inflammation in a similar pre-clinical model of CS-exposure<sup>2</sup>, indicates the potential utility of TRPV1 antagonists in the treatment of COPD, which is currently being evaluated in an ongoing COPD clinical trial. <h3>References</h3> Round. <i>Br J Clin Pharmacol. </i>2011;72:921–931 Baxter ATS. 2014;A2079
L'antibioprophylaxie par amoxicilline-acide clavulanique avant ponction d'une lésion kystique pancréatique sous échoendoscopie est-elle efficace?
Authors: P Leclercq, I Mohammedi, F Xuereb, D Breilh, R Legeron, E Zaoui, D Ribeiro, F Fumex, C Lefort, B Napoléon
Journal: Endoscopy (2012)

A l'heure actuelle, les recommandations d'antibioprophylaxie en cas de ponction sous échoendoscopie (EE) d'une lésion kystique pancréatique reposent sur peu d'arguments scientifiques et la diffusion de l'antibiotique préconisé au sein du tissu cible n'a jamais été étudiée. L'objectif de cette antibioprophylaxie est de prévenir une surinfection bactérienne de la cavité kystique ponctionnée. En France, c'est l'administration intraveineuse (iv) en une perfusion de 30 minutes d'amoxicilline 1g/acide clavulanique 200mg ou cefotaxime 1g iv, 30 minutes avant la ponction qui est recommandée par la Société Française d'Endoscopie Digestive (SFED). Le but de cette étude est de connaître le taux de pénétration de l'amoxicilline/acide clavulanique dans le liquide des kystes pancréatiques ponctionnés sous échoendoscopie.
A Half-Century of Prevention — The Advisory Committee on Immunization Practices
Authors: Jason L. Schwartz, Adel Mahmoud
Journal: New England Journal of Medicine (2014)

In 1964, after a vaccination program against polio, diphtheria, tetanus, and pertussis began, the Advisory Committee on Immunization Practices was created to advise the U.S. government on vaccination activities. The ACIP remains influential domestically and globally.
Deletion of<i>Men1</i>and<i>somatostatin</i>induces hypergastrinemia and gastric carcinoids
Authors: Sinju Sundaresan, Anthony J Kang, Michael M Hayes, Eun-Young K Choi, Juanita L Merchant
Journal: Gut (2016)

<h3>Background</h3> Gastric carcinoids are slow growing neuroendocrine tumours arising from enterochromaffin-like (ECL) cells in the corpus of stomach. Although most of these tumours arise in the setting of gastric atrophy and hypergastrinemia, it is not understood what genetic background predisposes development of these ECL derived tumours. Moreover, diffuse microcarcinoids in the mucosa can lead to a field effect and limit successful endoscopic removal. <h3>Objective</h3> To define the genetic background that creates a permissive environment for gastric carcinoids using transgenic mouse lines. <h3>Design</h3> The multiple endocrine neoplasia 1 gene locus (Men1) was deleted using Cre recombinase expressed from the Villin promoter (Villin-Cre) and was placed on a somatostatin null genetic background. These transgenic mice received omeprazole-laced chow for 6 months. The direct effect of gastrin and the gastrin receptor antagonist YM022 on expression and phosphorylation of the cyclin inhibitor p27<sup>Kip1</sup> was tested on the human human gastric adenocarcinoma cell line stably expressing CCKBR (AGSE) and mouse small intestinal neuroendocrine carcinoma (STC)-1 cell lines. <h3>Results</h3> The combination of conditional Men1 deletion in the absence of somatostatin led to the development of gastric carcinoids within 2 years. Suppression of acid secretion by omeprazole accelerated the timeline of carcinoid development to 6 months in the absence of significant parietal cell atrophy. Carcinoids were associated with hypergastrinemia, and correlated with increased Cckbr expression and nuclear export of p27<sup>Kip1</sup> both in vivo and in gastrin-treated cell lines. Loss of p27<sup>Kip1</sup> was also observed in human gastric carcinoids arising in the setting of atrophic gastritis. <h3>Conclusions</h3> Gastric carcinoids require threshold levels of hypergastrinemia, which modulates p27<sup>Kip1</sup> cellular location and stability.
FRI0243 Act-life study: patterns of tocilizumab use, and dosing among patients with rheumatoid arthritis in the clinical practice.
Authors: J. V. Tovar Beltrán, M. A. Guzmán Úbeda, I. Mateo Bernardo, R. García-Vicuña, M. Rodríguez-Gómez, M. Belmonte-Serrano, C. Marras, E. Loza Cortina, E. Pérez Pampin, V. Vila, A. Balsa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Currently, there is not substantial evidence about tocilizumab (TCZ) use for the treatment of rheumatoid arthritis (RA) outside of clinical trials. <h3>Objectives</h3> To describe usage patterns and dosage of TCZ, as well as its effectiveness and safety profile under real conditions of use. <h3>Methods</h3> This is a 12-month prospective, observational study carried out in 40 Spanish centers. The study population consisted of adult patients with moderate or severe RA and disease duration of ≥6 months who initiated treatment with TCZ after failure of at least one previous DMARD or TNF inhibitor. Final results are presented. <h3>Results</h3> A total of 379 patients were evaluated (83% female) with a median age of 57 years (47-66). At baseline, patients had mean disease duration of 12.1±8.2 years, 70.5% were rheumatoid factor positive and 68% anti-CCP positive. Mean baseline DAS28, SDAI, HAQ scores and CRP levels were 5.6±1.0, 22.9±15, 1.6±0.7 and 5.6±11.6 mg/dl, respectively. 78.4% of patients received TCZ in combination and 84.4% after prior use of biological agents. 97.6% of patients initiated TCZ at dose of 8 mg/kg. During the follow-up period, 68 (17.9%) discontinued TCZ treatment due to inadequate response (35.3%) and as result of adverse events (33.8%). At the end of follow-up, the mean DAS28 decreased significantly from baseline (5.6±1.0 <i>vs</i> 2.8±1.4; p&lt;0.001), and disease remission (DAS28&lt;2.6) was achieved in 51.3% of patients. Patients who received TCZ as first biological agent did not show a mean change in DAS28 score from baseline to final visit (delta-DAS28) significantly higher than in those previously treated with biological agents. No differences in delta-DAS28 were found when TCZ was administered as monotherapy or in combination with DMARDs. Based on EULAR response criteria, 65.2% of patients were good responders and 25.2% moderate responders. The main adverse events were infections (33.5%), gastrointestinal disturbances (21.4%), neutropenia (5.8%), elevation of liver transaminases (4.7%), and thrombocytopenia (1.1%). <h3>Conclusions</h3> Final results of this study indicate that in daily clinical practice, tocilizumab is a safe and effective treatment for moderate or severe RA, with the majority of patients having a good EULAR response and a disease remission being achieved in 51.3% of patients. Tocilizumab proves to have a similar efficacy profile regardless of the use pattern as monotherapy or in combination, and the line-biological option may be used. <b>Disclosure of Interest</b>: None Declared
SP0124 Advances in the Treatment of Spondyloarthritis
Authors: M. V. Navarro Compán
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Spondyloarthritis (SpA) is a group of chronic inflammatory disease with either predominantly axial symptoms of the spine and sacroiliac joints (axial SpA) or predominantly arthritis (peripheral SpA), being anlylosing spondylitis the major subgroup. The management of ankylosing spondylitis and other SpA such as psoriatic arthritis (PsA) is becoming more and more complex due to major progress in the last years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first stage in axial SpA and new studies have shown that continuous NSAID use revert the effects of inflammation on radiographic progression. The treatment with disease-modifying drugs, such as methotrexate, sulfasalazine, leflunomide, should be considered at an early stage in PsA and in combination with biologic therapies in case of inadequate response. Remarkable advances in axial and peripheral SpA are the development of new biologic therapies as well as their optimization and an early use of these drugs. Non-pharmacological treatment has also a positive effect on pain, mobility and function. In order to provide the best care to SpA patients, primary physicians should have knowledge about the different options and the best way to manage these patients. <h3>Disclosure of Interest</h3> None Declared
PTU-082 Right and extended right hepatic trisectionectomy: short and long term outcomes of 332 resections
Authors: G Marangoni, A Hakeem, R Storey, Z Hamady, H Sethi, G J Toogood, R K Prasad, J P A Lodge
Journal: Gut (2012)

<h3>Introduction</h3> Despite advances in surgical and anaesthetic techniques made over the last 2 decades, right hepatic trisectionectomy (RHT) is still a challenging procedure associated with higher rates of morbidity and mortality. Some patients may even require further extension of the resection to include part of segments II/III to achieve clearance (extended right hepatic trisectionectomy, ERHT). Aim of the study was to assess and compare the early and long-term outcomes of RHT and ERHT in our Unit. <h3>Methods</h3> From January 1993 to December 2010, 252 RHT and 80 ERHT were performed (n=332). Resection for colorectal liver metastases (CRLM), HCC, cholangiocarcinoma and other were 127, 43, 25 and 57 for RHT and 60, 3, 2, 15 for ERHT respectively. Mean age was 58.3 vs 57.9 and 57.1% vs 55% were males (RHT vs ERHT, p=NS). There were 61 caudatectomy in the RHT group and 15 in the ERHT (p=0.36, NS); vascular resection (IVC or PV) was performed in 61 and 10 cases (p=0.18, NS), biliary reconstruction was performed in 75 and 7 cases (p=0.01) and total vascular exclusion was necessary in 26 and 6 cases respectively (p=NS). The amount of functional hepatic remnant was based on intra-operative judgement. <h3>Results</h3> There were 23 in-hospital deaths (6.9%, RHT: 19, ERHT: 4; p=NS). Overall morbidity was 44% (RHT) and 47.5% (ERHT). Bile leak (17 vs 3), haemorrhage (14 vs 4), sepsis (33 vs 9), cardio-vascular events (12 vs 1) and renal failure (12 vs 3) did not differ among the two groups (RHT vs ERHT; p=NS). There were 42 (12.6%) post-hepatectomy liver failure (according to “50:50 criteria”): 23 in the RHT group and 19 in the ERHT group respectively (p=0.001). Mean hospital stay was 15.8 vs 17.1 days (RHT vs ERHT, p=NS). In the CRLM cohort, 1, 5 and 10 year survival was 78%, 47% and 39% vs 79%, 47% and 37% (RHT vs ERHT, p=0.93, NS). Median survival was 49 and 43.9 months respectively (p=NS) and median follow-up was 59.7 and 56.5 months (RHT vs ERHT). <h3>Conclusion</h3> RHT and ERHT are a major undertaking with significant morbidity and mortality but represent the only chance of cure in selected patients. Liver failure is higher in the ERHT group but does not translate in increased mortality. Long-term survival in CRLM is achievable and does not differ among the two groups. Extensive liver resections even beyond conventional boundaries should not be considered an absolute contraindication to surgery. <h3>Competing interests</h3> None declared.
WOUNDED BUT NOT BROKEN: OUTCOMES OF CARDIAC CONTUSION IN PATIENTS WITH A PRE-EXISTING HEART FAILURE
Authors: Odunayo Olorunfemi, John McNelis, Olatunde Ola, Oladimeji Akinboro, Gbolahan Ogunbayo, Anand Dayama, Melvin Stone
Journal: Journal of the American College of Cardiology (2016)