tbuckley/cabot-search huggingface dataset:
Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease
Authors: Michelle C. Williams, Amanda Hunter, Anoop S.V. Shah, Valentina Assi, Stephanie Lewis, Joel Smith, Colin Berry, Nicholas A. Boon, Elizabeth Clark, Marcus Flather, John Forbes, Scott McLean, Giles Roditi, Edwin J.R. van Beek, Adam D. Timmis, David E. Newby
Journal: Journal of the American College of Cardiology (2016)

In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621). In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)
Fibroblasts in Huntington's Disease
Authors: Ingeburg Goetz, Eugene Roberts, David E. Comings
Journal: New England Journal of Medicine (1975)

We investigated the growth of skin fibroblasts in tissue culture from 10 patients with Huntington's disease and eight healthy, unrelated controls. The patients' ages ranged from 34 to 56 years (mean, 48.5), and the mean duration of their clinical illness was 12.4 years. The controls' ages ranged from 32 to 64 years (mean, 42.3). No statistically significant differences were observed between the two groups in outgrowth of cells from the biopsies nor during subsequent routine culturing of fibroblasts. This contradicts the finding of earlier investigators that skin fibroblasts from patients with Huntingtons disease grow poorly in tissue culture. Matched pairs of Huntington's disease and control cultures grew at the same rate, but Huntingtons disease cells grew to a significantly higher maximal density (P < 0.02). This may indicate a genetically determined change in the cell surface or metabolic difference in Huntingtons disease. (N Engl J Med 293:1225–1227, 1975)
The Use of the Urinary Anion Gap in the Diagnosis of Hyperchloremic Metabolic Acidosis
Authors: D C Batlle, M Hizon, E Cohen, C Gutterman, R Gupta
Journal: New England Journal of Medicine (1988)

We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27±9.8 mmol per liter) and the urinary pH under 5.3 (4.9±0.03). In the eight patients with diarrhea the anion gap was also negative (-20±5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64±0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23±4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30±4.2, 12 patients), or selective aldosterone deficiency (39±4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification. (N Engl J Med 1988; 318:594–9.)
Case 83-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case An eighteen-month-old female child was admitted to the hospital because of an abdominal mass and jaundice. Six weeks previously there was an episode of intestinal grippe characterized by a fever of 103°F., diarrhea and occasional vomiting. The fever and diarrhea continued intermittently, and moderate anorexia developed. When the patient was seen by a pediatrician two weeks before entry examinations of the blood and urine were said to show icterus, and physical examination was negative. Examinations of the blood during the week before admission were said to demonstrate a decrease in the icterus. On the day before entry . . .
Abstract 837: Genetic alterations in <i>PIK3CA</i>, <i>AKT2</i> and <i>PTEN</i> gene associated with poor clinical outcome in oral squamous cell carcinoma
Authors: Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Ling-Ling Hsieh
Journal: Cancer Research (2010)

Abstract The PI3K/AKT pathway plays a fundamental role in the regulation of cell growth, division, survival, and, when disarranged, tumorigenesis. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) negatively regulates this pathway by acting as a lipid phosphatase. Genetic alterations in the PIK3CA, AKT2 and PTEN gene are common in the PI3K/AKT pathway in human cancers and associated with the aggressiveness of the disease. Thus, drug discovery activities have been directed over the past few years to identify compounds that effectively and specifically disrupt this pathway in tumor cells. To appraise the possible contribution of genetic alterations in the PIK3CA, AKT2 and PTEN genes in activating PI3K/AKT pathway in areca-quid (AQ) associated oral cavity squamous cell carcinomas (OSCCs), PIK3CA mutations, PIK3CA and AKT2 amplifications, and inactivation of PTEN via loss of heterozygosity (LOH), homozygous deletion (HD) and promoter methylation were examined in 153 OSCCs. The frequency of PIK3CA mutations, PIK3CA and AKT2 amplifications, and inactivation of PTEN was 3.21%, 40.52%, 15.69% and 15.03%, respectively. Increased number of gene alterations in the PIK3CA, AKT2 and PTEN gene (χ2 trend test: P = 0.003 and P = 0.027, respectively) was positively associated with lymph node metastasis and tumor differentiation. Based on the status of gene alterations in the PIK3CA, AKT2 and PTEN gene, a gene dosage effect on disease-free and overall survival was observed in patients who had undergone radiotherapy after surgery; however, this gene dosage effect was not significant in patients who had been treated with surgery alone. In the subset of patients received radiotherapy after surgery, patients who had one alteration in PIK3CA/PTEN/AKT2 gene had a poorer disease-free and overall survival, as compared to those with normal PIK3CA/PTEN/AKT2; and those had at least 2 alterations in PIK3CA/PTEN/AKT2 gene would further worsen the condition. Our study provides a rational for exploring treatment strategies that include radiotherapy combined with compounds blocking PI3K/AKT pathway. 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 837.
The Search for Genetic Links in ANCA-Associated Vasculitis and Its Variants
Authors: Maria C. Cid
Journal: New England Journal of Medicine (2012)

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis encompasses three distinct yet overlapping syndromes: granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and the Churg–Strauss syndrome. These vasculitides are lumped together, not only because of their clinical and histopathologic similarities but also because of their common serologic marker, ANCA, which may contribute importantly to the pathogenesis of vascular inflammation. ANCA encompasses two major specificities: proteinase 3, more commonly encountered in the context of granulomatosis with polyangiitis, and myeloperoxidase, more frequently occurring in association with microscopic polyangiitis and the Churg–Strauss syndrome.The pathogenesis of ANCA-associated vasculitis remains incompletely understood. Environmental, autoimmune, and genetic factors . . .
After all these years of SOD and endotherapy - how far have we come? The role of endoscopic treatment for acute recurrent pancreatitis (ARP) with sphincter of Oddi dysfunction (SOD)
Authors: D. Tan, S. Sherman
Journal: Endoscopy (2011)

The etiology of acute pancreatitis can be determined in the majority of patients. Alcohol and gallstones account for 60 % – 90 % of cases. Other causes include hypertriglyceridemia, hypercalcemia, drug reactions, trauma, genetics, neoplasia, surgery, endoscopic retrograde cholangiopancreatography (ERCP), etc. However, despite a careful history, physical examination, laboratory testing, and radiological evaluation, 10 % – 30 % of cases will have no obvious etiology and will be labeled as idiopathic acute pancreatitis (IAP) [1] [2] [3]. Patients with recurrent episodes of IAP are classified as having idiopathic acute recurrent pancreatitis (IARP). A structural cause for IARP will be found in the majority of patients who are further investigated with endoscopic ultrasound (EUS), ERCP with sphincter of Oddi manometry (SOM), bile crystal analysis (for those with the gallbladder in situ), and magnetic resonance imaging/cholangiopancreatography. The literature shows that sphincter of Oddi dysfunction (SOD) is the most frequent cause of IARP. Using ERCP with SOM as the gold standard for diagnosis, SOD has been manometrically documented in 15 % – 72 % of such patients [4] [5] [6] [7] [8] [9] [10] [11].
EFFECT OF BETA-BLOCKADE ON CARDIOVASCULAR EVENT RATES IN PATIENTS WITH ASYMPTOMATIC AORTIC STENOSIS
Authors: Casper N. Bang, Anders M. Greve, Anne B. Rossebø, Simon Ray, Kenneth Egstrup, Kurt Boman, Christoph Nienaber, Peter Okin, Richard Devereux, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2015)
Abstract 588: Silencing of MnSOD attenuates ATRA-induced neurofilament expression in neuroblastoma cells
Authors: Anne M. Silvis, Kelley Kiningham
Journal: Cancer Research (2011)

Abstract Differentiation therapy with retinoids is a means to treat high-risk neuroblastoma patients when the tumor has recurred after initial attempts of removal by surgery, radiation, and/ or chemotherapy. A metabolite of Vitamin A, all-trans retinoic acid (ATRA) is the main signaling retinoid in vivo and one of the most potent differentiation inducers for human neuroblastoma in vitro. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that converts the superoxide anion to hydrogen peroxide. Previously we have reported that ATRA increased MnSOD expression and activity in SK-N-SH neuroblastoma cells. However, our current study suggests that this upregulation may limit the ability of ATRA to induce differentiation. Treatment with ATRA upregulated the expression of neurofilament (an early marker of neuronal differentiation) as early as 48 hrs. Although MnSOD activity was not significantly increased by ATRA until 72 hrs, silencing of the MnSOD gene with siRNA enhanced neurofilament expression over that of cells infected with a control siRNA construct at 48 hrs. This suggests that even basal levels of MnSOD activity can attenuate an early marker of differentiation. We also demonstrated that ATRA decreased catalase expression and increased dichlorofluoroscein fluorescence, suggesting an increase in hydrogen peroxide. Therefore, these data suggest that rather than being scavenged by catalase, hydrogen peroxide may remain present in the cell after ATRA treatment to also limit the differentiation potential of the cells. Taken together, it is apparent that the alteration of redox status by retinoids may contribute to the modulation of genes which are involved in differentiation. (Funding: Centers for Biomedical Research Excellence 1P20RR020180 (KKK) and 5P20RR016477; WV-INBRE 5P20RR016477; WV-NASA 91-175B). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 588. doi:10.1158/1538-7445.AM2011-588
Abstract 4454: Cancer therapy using pulsed HIFU and a rose bengal derivative
Authors: Yoo-Shin Kim, Valentina Rubio, Rongmin Xia, Jianjun Qi, Zheng-Zheng Shi, Leif Peterson, Ching-Hsuan Tung, Brian E. O'neill
Journal: Cancer Research (2011)

Abstract High intensity focused ultrasound (HIFU) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. Unlike most sono-sensitizers, RB2 is not a photo-sensitizer, meaning it has no side effects associated with ambient light. In vitro tests have shown that a short treatment (less than 30s) of pulsed HIFU at 1 MHz with power sufficient for cavitation destroys &amp;lt;90% of breast cancer cells in suspension with 15uM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any significant impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine, NAC) reduced the effectiveness of the treatment, suggesting the possibility of an oxidative mechanism. In vivo tests using these same cells growing as a xenograft in mice were also done. Using similar treatment parameters in vivo necessitated the use of ultrasound contrast agents to initiate cavitation. When this was done, we were able to demonstrate rapid tumor regression for combination pulsed HIFU and RB2 treatments. RB2 was delivered in large doses of 25 mg/kg i.v. without any adverse side effects. In some animals, ablating a tumor with cavitation resulted the subsequent regression of both treated and control tumors. We believe it should be possible to develop this technology into an alternative safe and effective means of tumor ablation for breast cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4454. doi:10.1158/1538-7445.AM2011-4454
Response to ‘Geographical movement of doctors from education to training and eventual career post’
Authors: Catherine Tregoning, Jacky Hayden
Journal: Journal of the Royal Society of Medicine (2013)

Goldacre et al.’s above article1 was read with great interest. In 2008, The North Western Deanery completed a study looking at doctors’ career and retirement choices. This included analysis of the geographical movement of 1993–1996 medical graduates from The University of Manchester. Our group was substantially smaller than Goldacre et al.’s sample, with 22 medical trainees participating in interviews and 234 completing questionnaires. However, we too found that trainees often ultimately train or practise where either they or their partner originates from. An element of this was around the increasing need for childcare support from family. This may also offer part explanation for Goldacre et al.’s finding that among their sample more of the younger than older doctors ‘settled in the region of their family home’.

It was interesting that the authors also say, ‘Younger generations are more likely to take into account the preferences of their spouses than older generations.’

We found that while almost 45% of trainee participants located in the North West at the time of our study grew up in the region, almost a further 20% had a partner who originated from the North West. So in one-fifth of cases, the spouse’s possible preferred location had been followed.

We concluded that as it appears that medical trainees choose to subsequently live and work close to the location of family, then to improve retention of this group in the North West it is necessary to thus concentrate on recruiting students into medical schools locally.

Like the authors, we found there to be a lack of research on this topic.
Abstract 4536: Combination external beam and internal radiation via 131I-CLR1404 in the treatment of head and neck squamous cell carcinoma xenografts.
Authors: Jarob Saker, Eric Armstrong, Bryan Bednarz, Mohammed Farhoud, Abigail Besemer, Jamey Weichert, Paul Harari
Journal: Cancer Research (2013)

Abstract Radiotherapy (RT) is a central treatment modality for head and neck cancer (HNC). However, optimal outcome is commonly limited by the radiation tolerance of adjacent normal tissue structures. Radiation is sometimes valuable in the setting of locoregional tumor recurrence, however the risk of significant normal tissue toxicity is substantial with repeat irradiation and can have a profound adverse impact on patient quality of life. Although technical advances including intensity modulated radiotherapy (IMRT) can reduce normal tissue effects, the problem of repeat exposure of normal tissues to radiation is frequently limiting. The radiolabeled drug 124/131I-CLR1404 is a phospholipid ether analogue (PLE) that accumulates preferentially within malignant tumors and enables internal delivery of radiation. This allows a combination of external and internal radiotherapy delivery with a goal of improving treatment outcome without enhanced normal tissue toxicities. In this study, we characterized the ability of 131I-CLR1404 to augment RT response using xenografted mice harboring human squamous cell carcinomas (SCC). We determined tumor growth delay as well as tumor and normal tissue dose distribution of 131I-CLR-1404 via Monte Carlo simulation using PET data generated with 124I-CLR1404 imaging. Tumor growth delay was extended by 15.5 days using combined 3.7MBq 131I-CLR1404 and RT compared to RT or 131I-CLR1404 alone. In combination therapy, single dose administration of 7.4 MBq 131I-CLR1404 as well as split dosing with 2 x 3.7 MBq separated by one week showed the same additional growth delay of 27 days compared to single dose of 3.7 MBq. Monitoring drug distribution via PET/CT showed high tumor selectivity with a tumor-to-liver ratio of 6.2±0.65 and a tumor-to-muscle ratio of 6.7±0.21. These data illustrate the tumor selectivity of the CLR1404 PLE delivery platform as well as augmentation of tumor response with combined RT and 131I-CLR1404 treatment. De-intensification of external beam radiation dose, with attendant reduction in normal tissue toxicities so common in HNC patients represents a central objective to be tested in controlled clinical trials with the ultimate goal of improving treatment outcome and quality of life for HNC patients. Citation Format: Jarob Saker, Eric Armstrong, Bryan Bednarz, Mohammed Farhoud, Abigail Besemer, Jamey Weichert, Paul Harari. Combination external beam and internal radiation via 131I-CLR1404 in the treatment of head and neck squamous cell carcinoma xenografts. [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 4536. doi:10.1158/1538-7445.AM2013-4536
Intense Iodine Activity Caused by Mosquito Bite
Authors: Bin Liu, Gauri Tilak, Kevin Edwards, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2013)

A 12-year-old girl with a history of papillary thyroid cancer underwent radioiodine remnant ablation using 131I. Posttherapy whole-body 131I scintigraphy revealed not only the known activity in the neck but also increased activity in the superficial posterior right upper thigh. On further clinical evaluation, the patient was found to have a mosquito bite with surrounding hyperemia at the site of the abnormal activity.
THE CONTRIBUTION OF MYOCARDIAL LAYERS OF THE RIGHT VENTRICULAR FREE WALL TO RIGHT VENTRICULAR FUNCTION IN PULMONARY HYPERTENSION: ANALYSIS USING MULTI-LAYER LONGITUDINAL STRAIN ASSESSED BY TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Koya Ozawa, Nobusada Funabashi, Hiroyuki Takaoka, Nobuhiro Tanabe, Koichiro Tatsumi, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2016)
Notification about Early-Release Articles
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1999)

Five times during the past year, the Journal has released articles early by posting them on our site on the World Wide Web (http://www.nejm.org). The decision to release an article early is made together with the authors and in accordance with our policy that permits early release when a report may have immediate implications for clinical practice.1 All the articles released early last year had been peer reviewed and accepted for publication. The full text posted on the Web was identical to that published in print seven to nine weeks later. Readers can receive notification about articles released early by . . .
SP0057 Telemedicine - the Role of Technology in Supporting Patients' Choice
Authors: M.E. Tumim
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> A brief outline of Orkney9s demographics – facts about the hospital containing the dedicated telemedicine facilities and outlining the kind of health service that islanders receive. An explanation of how and why telemedicine was first set up for rheumatology in Orkney – it is believed to be the first telemedicine clinic for rheumatology in the UK. Putting this in a national context regarding NHS targets for treating patients closer to their homes. Explaining how telemedicine is becoming an increasingly useful tool for remote locations and services beleaguered by a scarcity of consultants – describing concerns, potential pitfalls - outlining advantages, e.g reducing the need for travel. Description of my own telemedicine experience in 2012. The technology – using high quality equipment and ensuring that the broadband width is good enough at both ends is paramount. The importance of trust between examiner and consultant – discussion with other health practitioners and patients about possibly extending the existing service. Summary – considering ways in which the telemedicine service in Orkney could be improved upon, and relating this to possible ways to improve the overall effectiveness of telemedicine in support of the patient9s choice. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6136