tbuckley/cabot-search huggingface dataset:
Abstract 21249: MRI Characterization of Tissue Injury Progression After Atrial Fibrillaton Ablation
Authors: Gaston R Vergara, Saulius Kalvaitis, Evgueni Kholmovski, Sathya Vijayakumar, Joshua Blauer, Christopher Gloschat, Kimberly Lilbok, Gene Payne, Nazem W Akoum, Chris McGann, Rob MacLeod, Nassir F Marrouche
Journal: Circulation (2010)

Introduction: Characterization of ablation lesion could help guide procedures by identifying viable tissue and scar gaps. In this study we showed MRI characterization of atrial tissue injury progression from catheter touch down to three months post ablation. Methods: Fifty patients underwent AF ablation under electro-anatomical guidance. Each patient was taken to a 3T MRI scanner immediately after ablation. High resolution LGE-MRI images of the left atrium (LA) were acquired 15 minutes after contrast injection. In addition, ten pigs were ablated in a 3T real-time MRI suite during scanning and T2 weighted and LGE-MRI images obtained during and immediately post-ablation respectively. Results: T2w HASTE images showed enhancement during ablation, initially in the area of RF delivery followed by spatial extension beyond this area. T2w enhancement was seen as early as 10–15 seconds post ablation. LGE-MRI imaging immediately post ablation often showed dark, non-enhancing regions of ablated tissue (Figure 3, A1-A...
Soundings: Illness behaviour
Authors: Kevin Barraclough
Journal: BMJ (2006)

We summarise the notes of patients joining the practice and put them on to the computer. The odd thing is that, often, if you have summarised the notes yourself, you almost seem to know the patient as they walk in through the door for the first time. In particular, you have a feel for their illness behaviour.

In general practice there is a high “noise to signal” ratio of symptoms that signify self limiting rather than significant disease. Frequently, particularly with an elderly population, a general practitioner may be told of 10 or more symptoms in one consultation. Each symptom potentially has an algorithm or guideline associated with it. And these patients are not a small subgroup of “somatisers.” They will be normal patients, usually slightly beyond middle age, who are becoming aware of their mortality and are no longer dismissing symptoms as minor, as they did 20 years ago.

Looking back, I suspect that the NHS survived because general practitioners investigated or referred hardly anything. They were, in David Haslam's memorable phrase, “the risk sink of the NHS.” They soaked up these symptoms at minimal cost. Sometimes this may have been merely because they were poor clinicians, but often it was because they knew their patients.

I realise that my own practice of investigation or referral is very much influenced by the knowledge of prior illness behaviour. It is only one of a myriad of other variables that come into the decision, but it is an important one. When I see a discharge summary of a patient admitted through casualty with alarming symptoms I am not surprised that all the scans were normal. I may know that, although the patient is delightful and hard working, the whole family “catastrophises” symptoms. Their described symptoms are never of moderate severity.

It would be difficult to include illness behaviour in any algorithm, or indeed, to explain your inaction under scrutiny if a patient turns out to have serious disease. Yet if such considerations are lost in future, if a patient is always assessed by a new doctor without knowledge of prior health seeking behaviour, I worry that the NHS will collapse under the weight of undiluted algorithmic investigation—and that people will spend much of their lives in radiology departments.
Paclitaxel poliglumex (PPX) and concurrent radiation for treatment of patients with esophageal or gastric cancer: A dose-ranging study
Authors: T. A. Dipetrillo, B. Chauhan, P. Akerman, T. Ng, T. Miner, D. Cruff, T. Rich, F. B. Oldham, A. Countouriotis, H. Safran
Journal: Journal of Clinical Oncology (2005)

4065 Background: Paclitaxel poliglumex (XYOTAX) is a drug conjugate that links paclitaxel to a biodegradable polymer, poly-L-glutamic acid. PPX is water-soluble and can be given as a 10-minute infusion. The hyperpermeable angiogenic vasculature and suppressed lymphatic clearance of tumors facilitate retention of macromolecules such as PPX within tumor space, resulting in higher intratumoral drug concentrations over prolonged periods. Preclinically, PPX has demonstrated tumor tissue radiation enhancement factors (REFs) from 4.0 to >8.0, versus 1.5–2.0 for paclitaxel; PPX did not radiosensitize normal tissue (Milas et al, Int J Rad Oncol, 2003). A phase I study of PPX and concurrent radiation was initiated to determine the maximum tolerated dose (MTD) for patients (pts) with esophageal or gastric cancer. Methods: Pts with esophageal or gastric cancer requiring chemoradiation for neo-adjuvant, adjuvant, or palliative treatment are eligible. Pts receive escalating dosages of PPX via 10-minute IV infusion on days 1, 8, 15, 22, 29, and 36 of each cycle with 50.4 Gy radiation (RT) in 28 fractions. Dose limiting toxicity (DLT) is defined as treatment-related grade 3/4 non-hematologic or grade 4 hematologic toxicity. Results: Fifteen pts have been treated over 5 dose levels of PPX: 40 mg/m2 (3 pts), 50 mg/m2 (4 pts), 60 mg/m2 (4 pts), 70 mg/m2 (3 pts), and 80 mg/m2 (1 pt). Nine pts had adenocarcinomas of the distal esophagus/GE junction, 3 had esophageal cancers extending to the stomach, and 3 had gastric cancer. PPX/RT has been used as definitive treatment for 12 pts with loco-regional disease, as adjuvant therapy for 2 pts with prior resection, and for local palliation for 1 pt with distant metastases. DLT has not been observed. Also, treatment-related, severe esophagitis has not been observed; prophylactic feeding tubes have not been required. Post-treatment endoscopy has shown tumor reduction in 11 of 12 pts, including three without residual cancer. Conclusions: PPX is a novel radiation sensitizer for patients with esophageal and gastric cancer. The MTD has not been reached; enrollment continues at 80 mg/m2/week with 50.4 Gy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics Cell Therapeutics Cell Therapeutics
Abstract 15787: Are Most Deaths After Percutaneous Coronary Intervention (PCI) Preventable? A Root-Cause Analysis
Authors: Javier Valle, Dean E Smith, David Childers, Anna M Booher, Daniel S Menees, Hitinder S Gurm
Journal: Circulation (2011)

Background: Prior studies suggest that most deaths in patients undergoing percutaneous coronary intervention (PCI) are related to procedural complications. Mortality associated with PCI has steadil...
...but not all do
Authors: W K C Morgan
Journal: BMJ (1995)

EDITOR,--John Bligh informs us that problem based learning is the cynosure of contemporary pedagogy.1 His editorial is replete with vogue phrases: “preferred active learning” (what is inactive learning?), “interpersonal skills,” “learning involvement,” etc. As a member of the academic staff of a Canadian medical school I can assure Bligh that not all Canadian academic staff share his admiration for McMaster University's teaching methods. Medical educators cannot avoid the responsibility for inculcating many facts, and medical students cannot be expected to …
Regulation of the coxsackievirus and adenovirus receptor (CAR) during epithelial-to-mesenchymal transition (EMT)
Authors: Markus Lacher, Christine Christian, W. M. Korn
Journal: Cancer Research (2004)

4592  CAR is the major receptor for subgroup C adenoviruses and therefore an important factor for the success of many adenovirus-based anti-cancer treatments. CAR is a transmembranic protein that takes part in the formation of the apical junctional complex. Loss of CAR expression in human cancers occurs frequently, in particular in high-grade tumors. We are investigating the molecular mechanisms regulating CAR expression in human malignancies in order to develop strategies to increase the efficacy of adenovirus-based therapies through pharmacological restoration of receptor expression. We examined alterations of CAR expression in mouse E4 skin cancer cells and the nontransformed mouse mammary gland epithelial cell line NmuMG during TGF-β induced EMT. TGF-β treatment of these cells resulted in down-regulation of CAR protein and mRNA expression which was mirrored by a dramatic reduction in infectivity with a luciferase-expressing, non-replicating adenovirus. To further characterize the nature of this regulation, we cloned the promoter regions of the human and mouse CAR gene. Using 5’ RACE, the transcriptional start sites in the TATA-less promoter were identified. The role of regulatory elements in the promoter region for repression of CAR transcription following EMT was characterized. Mutation or deletion of these elements restored CAR promoter activity in cells that had undergone EMT. Transcription factors were identified as candidates for mediating TGF-β dependent transcriptional repression of CAR in epithelial cells undergoing EMT.
Abstract 3503: Hydrogen Peroxide-Induced Afterdepolarizations are Dependent on Calmodulin Kinase II Signaling
Authors: Lai-Hua Xie, Fuhua Chen, James N Weiss
Journal: Circulation (2008)

Background: In the heart, hydrogen peroxide (H 2 O 2 ) has been shown to cause early afterdepolarizations (EADs) and triggered activity by impairing Na current (I Na ) inactivation. Since H 2 O 2 has been recently shown to activate Ca 2+ /calmodulin kinase II (CaMKII), and since CaMKII activation has also been reported to impair I Na inactivation and predispose to EADs, we hypothesized that CaMKII activation by H 2 O 2 may be an important factor in the genesis of EADs induced by oxidative stress. Methods and Results: Patch-clamped Fluo-4 AM-loaded rabbit ventricular myocytes were exposed to H 2 O 2 (0.1–1mM), which induced spontaneous EADs after 5–15 min. Both the I Na blocker tetrodoxtin (TTX, 10 μM) and the I Ca,L blocker nifedipine shortened AP duration (APD) and suppressed EADs. H 2 O 2 increased both peak and steady-state I Ca,L under square-pulse voltage clamp, and enhanced I Ca,L to a greater extent during the AP plateau than during the AP upstroke under AP clamp conditions. In addition, by prolonging the AP plateau and increasing Ca influx via maintained I Ca,L , H 2 O 2 -induced EADs frequently caused DADs delayed afterdepolarizations (DADs) due to spontaneous SR Ca release waves after repolarization. KN-93(1 μM), a CaMKII inhibitor, prevented H 2 O 2 -induced EADs (n=4), whereas the inactive analogue KN-92 did not (n=5). Conclusion: These findings indicate that H 2 O 2 -induced EADs depend on both impaired I Na inactivation to reduce repolarization reserve and enhanced I Ca,L to reverse repolarization. Intact CaMKII signaling is necessary for EAD generation in this setting, presumably via its actions on I Na and I Ca,L , although direct redox effects on other ion channels/transporters may also be important. Our observations support a link between increased oxidative stress, CaMKII activation and afterdepolarizations as triggers of lethal ventricular arrhythmias in diseased heart. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Blockade Of CD47 Using SIRPαFc: Role Of The Fc Region In Anti-Leukemic Activity and Tolerability
Authors: Robert A. Uger, Xinli Pang, Mark Wong, Violetta House, Karen Dodge, Stephane Viau, Noel T. Vigo, Debbie Tam, Tran Truong, Liqing Jin, Andrei V. Malko, Jenny Ho, Tatiana K. Prasolava, Jayne S. Danska, Jean C.Y. Wang, Penka S. Petrova
Journal: Blood (2013)
News
Authors: John Warden
Journal: BMJ (1990)

The cyclotron saga: the next chapterThe news that emerged last week that the Medical Research Council had stopped a clinical trial into neutron therapy again stirred into life the controversy surrounding the government's decision in 1988 to fund a new neutron therapy unit at St Thomas's Hospital in London.This decision aroused controversy because the Prime Minister had personally supported the provision of £6m (twice the government's yearly budget for cancer research) to the Cyclotron Trust, which was made without consultation with- and against the protests of-cancer experts in the United Kingdom (BMJ 1988;297:1625).The United Kingdom Coordinating Com- mittee on Cancer Research, which repre- sents the cancer research funding agencies, argued at the time that neutron therapy was unproved and produced worrying side effects and that the very least the government should do was to await the outcome of trials at Clatterbridge (the site of Britain's only current therapeutic cyclotron) before com- mitting such a large sum.Now that one of the Clatterbridge trials has been stopped many cancer experts are hoping that the govern- ment will reverse its decision over the St Thomas's cyclotron.That neutron therapy might be effective for treating some cancers was first shown in the United Kingdom at Hammersmith Hospital in the 1970s.But the adequacy of the trial design was later questioned and subsequent trials in Edinburgh failed to show any significant benefit from neutron therapy and, more worryingly, showed a high rate of late and unpleasant complications.To resolve this conflict of evidence the Medical Research Council set up two trials of neutron therapy at Clatterbridge Hospital-one for cancers of the rectum, bladder, and cervix and one for advanced cancer of the head and neck.In March this year the council stopped the trial into pelvic cancers when an inde- pendent data monitoring group reviewed all the data from the trial and concluded that neutron therapy could show no pos- sible survival advantage over photon therapy -the conventional and much cheaper treat- ment.The trial had been running only since 1986 and had accrued 144 patients overall.Hence, almost certainly, this must mean that morbidity and/or mortality were significantly higher among those treated with neutrons.According to the council, the full details of the trial will not be submitted for publication until later this year.In the mean time the head and neck cancer trial, a multicentre trial in collaboration with North American centres, continues.According to a spokesman, the Depart- ment of Health is now considering the impli- ore are the bodies hidden?In a completed but unpublished studvfor the MKC
Abstract 2550: N-terminal Pro-brain Natriuretic Peptide-defined Cardiomyopathy in Doxorubicin-treated Children with Acute Lymphoblastic Leukemia
Authors: Steven E Lipshultz, Stuart R Lipsitz, Rebecca E Scully, Tracie L Miller, Elly Barry, Nader Rifai, Virginia M Dalton, Lewis B Silverman, Steven D Colan, Barbara L Asselin, Uma Athale, Luis A Clavell, Eric Larsen, Albert Moghrabi, Yvan Samson, Marshall A Schorin, Richard D Gelber, Stephen E Sallan
Journal: Circulation (2007)

Background: Doxorubicin damages heart muscle, placing long-term survivors of childhood cancer at elevated risk of cardiac dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP), an independent predictor of mortality and cardiovascular events in other populations, may serve to indicate cardiomyopathy prior to irreversible damage in this population. Methods: To determine the diagnostic value of NT-proBNP in children receiving doxorubicin, the NCI Dana-Farber Cancer Institute ALL Consortium collected serial serum samples and echocardiograms from children with ALL between 1995 and 2000 randomized to receive doxorubicin alone (dox; n = 74; 1203 samples; median age = 6.4 yrs; 30 mg/m 2 /dose for 10 doses) or doxorubicin preceded by the cardioprotectant dexrazoxane (dex/dox; n = 80; 1338 samples; median age = 7.1 yrs; 300 mg/m 2 /dose). Results: Marked NT-proBNP elevation (NT-proBNP ≥ 100 pg/ml if age ≥ 1; proBNP ≥ 150 pg/ml if age &gt; 1) was seen at baseline (treatment day 0; dox alone = 82.5% of patients abnormal; dex/dox = 87.4%; p = 0.527). During treatment, the percentage of patients with abnormal NT-proBNP levels fell to a minimum of 35.8% in the dox only group and 16.4% in the dex/dox group ( p &lt; 0.001) before rising progressively at the end of treatment (treatment day 220; dox only = 70.8%; dex/dox = 5.3%; p &lt; 0.001). After controlling for treatment, a patient with abnormal NT-proBNP six months after the start of doxorubicin had 2.39 times the odds of having myocardial injury as indicated by elevated cardiac troponin T (cTnT ≥0.01 ng/mL; OR = 2.39; 95%CI 1.156 - 4.946; p = 0.019). Further, at any given time and for either treatment, a patient with abnormal NT-proBNP had 2.36 times the odds of having abnormal LV fractional shortening (OR = 2.36; 95%CI 1.026 - 5.449; p = 0.047). Conclusion: Elevated serum NT-proBNP was significantly related to cumulative unprotected doxorubicin dose, left ventricular fractional shortening, and cTnT during doxorubicin therapy. A much higher percentage of patients exhibited levels of NT-proBNP suggestive of cardiomyopathy than showed death of cardiomyocytes as indicated by elevated cTnT levels. This might allow the testing of individualized preventative therapy for cancer patients at high risk for long-term cardiotoxicity.
Abstract 4130: Applicability Of Left Ventricular Hypertrophy Electrocardiographic Criteria In Professional Athletes
Authors: Nelson Samesima, Carlos A Pastore, Luciana D de Matos, Fernanda F Fumagalli, Mariane V Ferreira, Euler V Garcia, Luciene F Azevedo, Nancy M Tobias, Renata d Liparizi, Patricia S Perlingeiro, Carlos E Negrão
Journal: Circulation (2008)

Introduction. The widely known electrocardiographic criteria for diagnosing left ventricular hypertrophy (LVH) use QRS complex voltages to define whether there is left ventricle enlargement or not. Mild myocardial hypertrophy is detected in many professional athletes and this is a consequence of their daily intensity of training. Thus it is not unusual that athlete’s ECGs show large QRS voltages with normal hearts. Objective. To evaluate the applicability of the usual electrocardiographic criteria for LVH - Sokolow-Lyon, Romhilt-Estes, Cornell and Gubner - in a population of professional athletes. Methods. The four LVH criteria for diagnosing LVH were applied to analyse ECGs of 107 professional athletes (71% soccer players, 29% marathonists, all male, age 25± 10 years, training for 9± 8 years) by the same observer unaware of echocardiographic results. ECG was considered to be indicative of LVH if: Sokolow-Lyon ≥35mm (V 1or 2 S wave+V 5or 6 R wave); Romhilt-Estes score ≥5 points (frontal plane: R or S waves ≥ 20mm, horizontal plane: R or S waves ≥ 30mm, Morris indices, V 5or 6 strain pattern, left axis deviation ≥ − 30°, intrinsecoid deflection ≥ 0.04s, QRS duration ≥ 0.10s) ; Cornell ≥ 28mm (aV L R wave + V 3 S wave); Gubner ≥ 22mm (D I R wave + D III S wave). Hypertrophy was considered whenever: LV diastolic diameter ≥ 60mm and/or septum ≥ 13mm and/or LV posterior wall ≥ 13mm. Kruskal-Wallis was used to statistically analyse quantitative variables, corrected chi-square test for categorical variables. Significance level: p ≤ 0.05. Results. Romhilt-Estes showed the best results (75% sensitivity, 84% specificity, 16 false-positives, 1 false-negative), and was the only criteria with statistical significance (p = 0.047). Sokolow-Lyon showed 100% sensitivity, 15% specificity, p = 0.545, 88% false-positives, 0% false-negative. Cornell and Gubner showed 25% and 0% sensitivity, 95% and 99% specificity, p=0.205 and p = 0.449, respectively. Conclusion. In this male population of professional athletes, Romhilt-Estes score proved to be the best criterion for identifying left ventricular hypertrophy, while Sokolow-Lyon criterion did not discriminate normal from abnormal hearts. Cornell and Gubner criteria should not be used in this population because of their low sensitivity.
Abstract 15980: Smoking, Smoking Cessation and Risk of Sudden Cardiac Death in Women
Authors: Roopinder K Sandhu, Monik Jimenez, Stephanie E Chiuve, Stacey A Kenfield, Usha B Tedrow, Christine M Albert
Journal: Circulation (2011)

Background: Smoking is a strong and modifiable risk factor for sudden cardiac death (SCD). However, few prospective studies have examined the impact of quantitative cigarette consumption and smokin...
Abstract 12314: The Long-Term Effect of Coronary Atherosclerosis and Apnea Hypopnea Index During Rapid Eye Movement on Posttraumatic Stress Disorder
Authors: Naser Ahmadi, Fereshteh Hajsadeghi
Journal: Circulation (2014)

Introduction: Posttraumatic-stress-disorder(PTSD) is associated with subclinical-atherosclerosis as well as rapid-eye-movement(REM) apnea-hypopnea-index(AHI). This study investigated the relation of coronary-atherosclerosis measured by coronary-artery-calcium(CAC), REM-AHI with cardiovascular(CV)-mortality in PTSD. Hypothesis: There is a direct relation between CAC and REM-AHI with increased CV-mortality in PTSD. Methods: This study is consist of 634 veterans without-known-CAD(age:58±11years,86%men) underwent CAC-scanning and overnight poly-somnography for clinical-indications. Psychological-health-status(PTSD vs. non-PTSD)was measured and they were followed for median of 36-months. Multivariable-Cox-regression-analyses were employed to assess the relation of REM-AHI and CAC, with CV-mortality in PTSD. Results: At follow-up (figure 1), the death-rate was higher in the PTSD(17%) than non-PTSD(10.4%)(p=0.001). Regression-analyses revealed a significant-linkage between PTSD and CAC as well as PTSD and REM-AHI with CV-mortality. The relative-risk of CV-mortality was 5.72(95%CI:2.46-13.34,p=0.0001) in PTSD and CAC&gt;0 as compared to non-PTSD with CAC=0. Similarly, the relative risk of CV-mortality was 3.22 (95%CI:1.17-8.85, p=0.02) in PTSD and REM AHI≥30 as compared to non-PTSD with REM AHI0 which was more prominent in PTSD(p=0.001). A significant linkage of CAC and REM-AHI with increased CV-mortality in PTSD was noted in which the relative-risk of CV-mortality in PTSD was 6.44 (95%CI:3.64-11.37,p=0.001) in combined CAC&gt;0 and REM AHI≥30 as compared to non-PTSD. Conclusions: 1)PTSD is associated with the coronary-atherosclerosis and increased CV-mortality, 2)PTSD is associated with REM obstructive-sleep-apnea and predicts CV-mortality and 3) There is an independent significant linkage of PTSD with REM obstructive-sleep-apnea as well as coronary-atherosclerosis, and increased risk of CV-mortality.