tbuckley/cabot-search huggingface dataset:
AB0980 Is Inflammation (Power Doppler Signal) Associated to the Development of New Bone Erosions in Hand Osteoarthritis? A Longitudinal Ultrasound Study
Authors: L. Mancarella, O. Addimanda, P. Pelotti, E. Pignotti, L. Pulsatelli, R. Meliconi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ultrasound (US) detected power Doppler signal (PDS) is frequently observed in erosive hand osteoarthritis (EHOA). So far all studies on US detected synovitis and structural damage in HOA have been cross sectional studies (1). Therefore not able to evaluate the time association between synovitis (PDS) and bone erosions along the lines of what has already been soundly demonstrated in patients with RA both at patient and joint levels. <h3>Objectives</h3> We performed a longitudinal study to evaluate the relationship between PDS at basal evaluation and new bone erosions detected after about 4 years in joints of patients with HOA. <h3>Methods</h3> In the first evaluation (2), we studied 35 subjects (10 normal controls, 12 with non-EHOA and 13 with EHOA). After a mean of 3.9 years, we performed an X-ray and US re-evaluation of both hands of 32 of the original 35 patients (3 subjects were lost at follow up). We evaluated the time relationship between the presence of PDS at the first study (Time 0: T0) and the development of new bone erosions in the second examination (Time 1: T1). Therefore we took into consideration only the joints which were without bone erosions at baseline and we considered the percentage of the newly detected erosions: radiographic central and marginal erosions, US detected erosions. We performed statistical analysis by General linear model and univariate analysis corrected for patient, age, sex and BMI. <h3>Results</h3> We found a significant increase in the percentages of all types of erosions comparing the first and the second imaging evaluation (data not shown). We found that the presence of PDS was significantly associated with a higher prevalence of new central erosions only in proximal interphalangeal (PIP) joints (Table 1). In addition, the presence of PDS was associated with new US detected erosions only in distal interphalangeal (DIP) joints (Table 2). No association between PDS and the development of new radiographic marginal erosions was observed. <h3>Conclusions</h3> Our study demonstrates only partial association between the presence of active synovitis, as detected by PDS, and the subsequent development on new bone erosions. <h3>References</h3> Kortekaas MC et al. In erosive hand osteoarthritis more inflammatory signs on ultrasound are found than in the rest of hand osteoarthritis. Ann Rheum Dis. 2013 Jun;72(6):930-4. Mancarella L et al. Ultrasound-detected synovitis with power Doppler signal is associated with severe radiographic damage and reduced cartilage thickness in hand osteoarthritis. Osteoarthritis Cartilage. 2010 Oct;18(10):1263-8. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4928
Heavy Phenacetin Use and Bladder Cancer in Women Aged 20 to 49 Years
Authors: Joyce M. Piper, James Tonascia, Genevieve M. Matanoski
Journal: New England Journal of Medicine (1985)

We investigated the use of analgesics containing phenacetin or acetaminophen in 173 young women with urinary bladder cancer and 173 matched controls. The cases, who were 20 to 49 years old at the time of diagnosis of cancer, were 6.5 times more likely to report regular use of analgesics containing phenacetin at least one year before diagnosis than were their matched controls (odds ratio, 6.5; 95 per cent confidence interval, 1.5 to 59.2). Among the 15 women (13 cases and 2 controls) reporting regular use of phenacetin-containing drugs, 8 of the cases and 1 of the controls reported daily use for over one year (P = 0.04). Excessive use of analgesics containing acetaminophen was not reported. The increased risk of bladder cancer in young women who regularly used phenacetin-containing products remained present after adjustments for all other identified risk factors.
Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation
Authors: John P. Kress, Anne S. Pohlman, Michael F. O'Connor, Jesse B. Hall
Journal: New England Journal of Medicine (2000)

Continuous infusions of sedative drugs in the intensive care unit may prolong the duration of mechanical ventilation, prolong the length of stay in the intensive care unit and the hospital, impede efforts to perform daily neurologic examinations, and increase the need for tests to assess alterations in mental status. Whether regular interruption of such infusions might accelerate recovery is not known.
Abstract SY09-02: A new <i>C. elegans</i> cell death pathway: Implications for neurodegeneration and cancer
Authors: Shai Shaham
Journal: Cancer Research (2011)

Abstract Programmed cell death is an essential process during metazoan development. During development of the nematode C. elegans nearly all cells slated to die activate caspases and undergo stereotypical morphological changes, including chromatin compaction and cell shrinkage. The male-specific linker cell, however, is an exception. The linker cell leads the migration of the developing gonad and once migration is complete the cell dies. Strikingly, mutations in the genes ced-3/caspase, ced-4/Apaf-1, egl-1/BH3-only, or ced-9/BCL2, the main regulators of apoptosis in C. elegans, do not affect linker cell death. Linker cell death must, therefore, be controlled by a novel program. Electron micrographs of dying linker cells reveal nonapoptotic features, including nuclear membrane invaginations, absence of chromatin condensation, and swelling of mitochondria and the endoplasmic reticulum. Similar features are seen in dying vertebrate neurons during development and in neurons that die from polyglutamine-induced toxicity as occurs in Huntington's disease and other spinocerebellar ataxias. To understand the molecular basis of linker cell death we sought genes that regulate the process. We have identified over 15 genes controlling linker cell demise and have begun to place these in genetic pathways. Our results demonstrate that linker cell death is initiated by a cell-autonomous transcriptional program that induces the expression of genes required to promote linker cell death. One transcriptional target, the gene pqn-41, has been studied in detail. pqn-41 encodes a 2100 amino-acid protein with a C-terminal domain in which 151 of 427 amino acids are glutamine. pqn-41 expression is induced in the linker cell just prior to onset of death, and the protein partitions to both nucleus and cytoplasm, accumulating in cytoplasmic puncta. Importantly, an endogenous transcript encoding only the polyglutamine domain of pqn-41 is sufficient to rescue pqn-41 mutants. pqn-41 functions together with a MAPK pathway and a pathway regulated by the microRNA let-7, whose expression is often disrupted in human lung cancer. Our results demonstrate the existence of a new metazoan cell death pathway and raise the possibility that neurodegenerative diseases resulting from polyglutamine expansions may inappropriately activate this program to cause neuronal loss. 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 SY09-02. doi:10.1158/1538-7445.AM2011-SY09-02
P141 Outpatient Management of Suspected Pulmonary Embolism at a District General Hospital; A Two Month Review
Authors: JA Benjamin, A Griffiths, S Power, E Kidner
Journal: Thorax (2012)

<h3>Background</h3> Studies have suggested that outpatient (OP) management of suspected pulmonary embolism (PE) is feasible.<sup>1</sup> At our DGH (pop<sup>n</sup> 289,400) the decision to manage a suspected PE as an OP is made clinically by the admitting physician. The aims of our study were To ascertain the proportion of patients who underwent CTPA investigation that were managed as outpatients and subsequent nights saved. To identify any further patients that could have been managed as OP and potential nights that could have been saved. To determine if the outpatients met the current criteria for ambulatory management of PE. <h3>Methods</h3> RADIS was used to collect all CTPA’s performed between 1st September 2011 and 31st October 2011.Notes were requested. <h3>Inclusion criteria</h3> Ambulatory, normal heart rate, respiratory rate, blood pressure and oxygen saturations (on air),any patient who was managed acutely as an OPPESI Score &lt; 85.<sup>2</sup> <h3>Exclusion criteria</h3> Any pre-existing in-patient that had a CTPA ordered where the primary admission (and reason for in-patient stay) was not for suspected PE, any patient who had their CTPA on the same day of discharge, OP CTPA where waiting time was &gt; 2 weeks. PESI Score &gt; 85.<sup>2</sup> <h3>Results</h3> For the above period 105 CTPA’s were performed. Average time from request to CTPA was 4.1 hours (1–21 hours.) Figure 1 shows the excluded patients. 15 patients were included; 7 were female, average age 47 years(18–78 years).All had a PESI score &lt;85.11 were investigated as outpatients (1 PE +ve) and 4 were kept as inpatients(2 PE +ve). The 11 managed as outpatients resulted in 17 nights saved. The 4 inpatients (if managed as OP) could have saved an additional 6 nights. <h3>Conclusion</h3> Over a 2 month period at our DGH most suspected PE patients (suitable for ambulatory care) are being identified resulting in significant (17 nights) bed savings. Hogg K et al, Emerg Med J 2006; 23:123–127. Aujesky D et al, AJRCCM 2005; 172(8):1041.
PTU-219 Intraoperative endoscopy: the first single-centre UK experience
Authors: K Evans, S Akula, I C Cameron, D S Sanders, M E McAlindon, R Sidhu
Journal: Gut (2012)

<h3>Introduction</h3> Intra-operative enteroscopy (IOE) is the gold standard for examination of the small bowel. However, with the invention of capsule endoscopy (CE) and double balloon endoscopy (DBE), the role of IOE has been questioned. Our aim was identify the indications for IOE and associated morbidity and mortality. We also made comparisons between CE and IOE. <h3>Methods</h3> All patients that underwent IOE between 2003 and 2011 were included. Data collected included demographics, clinical indications, co-morbidity, transfusion requirements, findings at IOE and subsequent follow-up. <h3>Results</h3> There were 17 IOEs, 8 males, with a mean age of 57 years (range 34–93). The median follow-up period was 9 months (range 0–48 months). The indication was iron deficiency anaemia (IDA) in all patients (occult bleeding (n=10) and overt bleeding (n=7)). Ten patients were transfusion dependent. The median haemoglobin pre-IOE was 7.7 g/dl (SD 1.4). 71% (n=12) had significant co-morbidity which included ischaemic heart disease, diabetes and bronchiectasis. Small bowel investigations prior to IOE included DBE (n=9) and CE (n=16). Two patients had therapeutic intervention at DBE, both argon plasma coagulation (APC) to angiodysplasia. In seven patients the abnormality on CE was not reached at DBE. The diagnostic yield for IOE was 88% (15/17). In two patients, the IOE was normal. Findings at IOE included Meckels diverticulum (n=2), arteriovenous malformations (n=7), small bowel tumours (n=3; benign glomus tumour, leiomyoma and carcinoid), bleeding point at surgical anastamosis (n=2; post hepatectomy and at a transplanted pancreatic bed) and small bowel ulceration secondary to NSAIDs and nicorandil. Intervention at IOE occurred in 82% (n=14). These included 10 small bowel resections, two APC, one revision of anastamosis, one oversewing of angiomata. While the morbidity rate was 18% (n=3) with two post-operative bleeds requiring transfusion and a seizure secondary to hyponatraemia, there were no deaths within 30 days. Evidence of recurrent GI bleeding occurred in four patients all of whom have lower transfusion requirements than before, 1 being on tranexamic acid, and 1 on somatostatin analogue. In the two patients with a normal IOE; the patient with IDA remains well 6 months post IOE while the second patient with diarrhoea and pain remains symptomatic without a diagnosis. A comparison of CE against IOE as the gold standard provided CE with a sensitivity, specificity, positive predictive and negative predictive values of 87%, 100%, 100% and 33% respectively. <h3>Conclusion</h3> IOE has a high diagnostic yield (88%) with a significant proportion having intervention at IOE. There remains an important role for IOE in a select group of patients with transfusion –dependent anaemia. <h3>Competing interests</h3> None declared.
S94 Ultrasound measurement of quadriceps wasting in early chronic obstructive pulmonary disease and its relationship with daily physical activity
Authors: D. Shrikrishna, R. Tanner, J. M. Seymour, M. Patel, B. A. Connolly, Z. A. Puthucheary, S. L. F. Walsh, S. A. Bloch, P. S. Sidhu, N. Hart, J. Moxham, M. I. Polkey, N. S. Hopkinson
Journal: Thorax (2011)

<h3>Introduction</h3> Quadriceps weakness is recognised as an important complication of COPD but few data exist about loss of muscle bulk in early disease. We hypothesised that quadriceps wasting, measured by ultrasound rectus femoris cross-sectional (USRF<sub>CSA</sub>), would be observed in patients with mild COPD compared to healthy age-matched subjects and that this would correlate with daily physical activity levels. <h3>Methods</h3> Rectus femoris cross-sectional area was measured using ultrasound (USRF<sub>CSA</sub>) and daily physical activity (step count and physical activity level—PAL) recorded using a multisensor biaxial armband accelerometer. Fat free mass index (FFMI) and the impedance ratio (Z<sub>200</sub>/Z<sub>5</sub>) were determined by bioelectrical impedance analysis. Quadriceps maximum voluntary contraction (QMVC) was used as a measure of strength. <h3>Results</h3> 150 patients with stable COPD, GOLD stage I (n=38), II (n=38), III (n=37) and IV (n=37), mean (SD) age 66 (9) years, 54% male and 40 age-matched healthy subjects participated in the study. USRF<sub>CSA</sub> was significantly reduced in stage I COPD patients compared to controls (530 mm<sup>2</sup> vs 640 mm<sup>2</sup>; p=0.0002) (Abstract S94 figure 1); USRF<sub>CSA</sub> was also reduced in stages II (526 mm<sup>2</sup>), III (503 mm<sup>2</sup>) and IV (509 mm<sup>2</sup>) disease (p=0.0001). Daily physical activity was reduced in stage I patients (steps; p&lt;0.0001, PAL; p=0.002) and stage II–IV COPD (steps and PAL; p&lt;0.0001) compared to healthy subjects. Using multivariate linear regression, USRF<sub>CSA</sub> (p=0.0003), FFMI (p=0.0003) and the impedance ratio (p=0.001) were all independent predictors of quadriceps strength in COPD. In stage I patients, only USRF<sub>CSA</sub> was shown to be independently associated with daily physical activity (steps, p=0.03; PAL, p=0.003), while in stage II–IV disease, FEV<sub>1</sub>% predicted was retained as the only independent correlate with daily physical activity (steps and PAL, p&lt;0.0001). <h3>Conclusions</h3> Quadriceps wasting identified by USRF<sub>CSA</sub> exists in patients with early, as well as advanced, COPD when compared to healthy age-matched controls. Quadriceps bulk is associated with daily physical activity independent of airflow obstruction, in early but not advanced disease. Our data suggest that, rather than being an end-stage phenomenon, quadriceps wasting is present in a substantial minority of COPD patients and is related to physical inactivity in the absence of severe airflow limitation.
P686Abnormal electrical activity of remodelled T-tubules promotes asynchronous Ca2+ release in heart failure
Authors: C Crocini, R Coppini, C Ferrantini, P Yan, L Loew, C Tesi, C Poggesi, E Cerbai, F S Pavone, L Sacconi
Journal: Cardiovascular Research (2014)

Action potential (AP), via the transverse axial tubular system (TATS), synchronously triggers uniform Ca2+-release throughout the cardiomyocyte. Cardiac diseases associated with TATS structural remodeling preclude a uniform Ca2+-release across the myocyte, contributing to contractile dysfunction. Here, we combined the advantage of an ultrafast random access multi-photon (RAMP) microscope with a double staining approach to optically record AP in several TATS elements and, simultaneously, the corresponding local Ca2+-transient. In rat control cardiomyocytes, although AP was uniform between surface sarcolemma (SS) and t-tubules (TT) at steady-state stimulation, we observed a non-negligible beat-to-beat variability of local Ca2+-transient amplitude and kinetics. This variability was significantly reduced applying 0.1 μM Isoproterenol, which increases the open probability of Ca2+-release units. Ca2+ sparks, detected at times throughout the TATS, did not induce any membrane potential variation in the surrounding tubular elements. In a rat model of post-ischemic heart failure (HF), we previously demonstrated that some tubular elements fail to propagate AP (AP-; Sacconi PNAS 2012). Here, we found that those AP- tubules displayed a slower and reduced local Ca2+-transient compared to electrically coupled tubules (AP+). Consistently, in a model of acute detubulation, tubules that do not conduct AP showed a local reduction and delay of Ca2+-transient rise. In addition, variability of Ca2+-transient kinetics was increased in HF. Finally, AP- tubular elements, occasionally exhibited spontaneous depolarisations of various amplitude and kinetics. These events were never accompanied by local Ca2+-release in the absence of pro-arrhythmogenic stimuli, while they could induce local Ca2+-release in the presence of 0.1 μM Isoproterenol. Simultaneous recording of AP and Ca2+-transient allows us to probe the spatio-temporal variability of Ca2+-release, whereas the investigation of Ca2+-transient in HF discloses an unexpected uncoupling between t-tubular depolarization and Ca2+-release in remodelled tubules. This work was supported by the European Union 7th Framework Program (FP7/2007- 2013) under grant agreement n° 284464, 241526, by the Italian Ministry of University and Research (NANOMAX), and by Telethon-Italy (GGP13162).
Abstract 4156: Detection of lung cancer from plasma using the biosignature of circulating microvesicles
Authors: Andrea Tasinato, Gherici Hassaine, Elodie Ristorcelli, Wang-Juh Chen, Christine D. Kuslich
Journal: Cancer Research (2011)

Abstract Circulating microvesicles (cMV) are cell-derived structures that are abundantly present in the blood. Tumor cells produce large quantities of cMV, and their abundance has been shown to correlate with tumor invasiveness and resistance to therapy. This study attempts to understand the origin, composition, and potential clinical utility of cMV, analyzing their protein composition in patients with non-small cell lung cancer (NSCLC) and identifying a cMV-based biosignature that can be used to predict the presence of tumors from a blood sample. cMV were isolated from plasma samples that were obtained from an initial cohort of 65 patients with NSCLC and from 46 control samples. A discovery panel of 63 specific biomarkers was used to develop an assay with high specificity and sensitivity based on 4 cMV surface proteins. Using a novel cMV-based multiplexed analysis platform we optimized a threshold level for 4 significant cMV subpopulations to effectively distinguish lung cancer patients from controls. The multiplex assay included 1 general cMV marker (CD81) and 3 lung cancer-associated biomarkers: the lung epithelial C-type lectin members SPD and SPA, plus the sialoprotein osteopontin. The decision tree analysis, based on specific cut offs, showed a sensitivity of 81% and a specificity of 90%. These results provide initial evidence that the identification of biosignatures in distinct subpopulations of cMV may offer a powerful blood-based approach for the detection and monitoring of specific disease states, such as NSCLC. 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 4156. doi:10.1158/1538-7445.AM2011-4156
P191 Beta-2 adrenoceptor genotype and response to propranolol in patients with persistent asthma: Abstract P191 Table 1.
Authors: WJ Anderson, PM Short, JLR Lipworth, A Manoharan, CNA Palmer, BJ Lipworth
Journal: Thorax (2013)

<h3>Background</h3> The arginine-16-glycine (Arg16Gly) beta-2 adrenoceptor (ADR) polymorphism is associated with worse outcomes in patients exposed to regular beta-agonists. We therefore wished to know if Arg16Gly conferred a similar effect in response to beta-antagonists in asthma. <h3>Methods and observations</h3> We have performed a retrospective composite analysis of two randomised controlled trials looking at effects of Arg16Gly on the chronic response to propranolol in n = 25 mild to moderate corticosteroid treated persistent asthmatics. We evaluated chronic dosing effects of propranolol given for at least 4 weeks (80mg dose at least 2 weeks) on pulmonary function (FEV1, FEF25–75, total airway resistance at 5Hz: R5) and on salbutamol FEV1 recovery post histamine challenge. Comparisons were made between genotypes comprising one or two copies of Arg (i.e. ArgArg or ArgGly n = 15, FEV1 = 91.1%, FEF25–75 = 58.3%) vs. no copies of Arg (i.e. GlyGly n = 10, FEV1 = 94.1% FEF25–75 = 60.0%). <h3>Results</h3> Data are shown in table as change from baseline (i.e. pre vs. post propranolol as means and SEM) within each genotype. Within the Arg genotype there were significant effects of propranolol on FEV1, FEF25–75 and R5 as well as significant blunting of salbutamol response, while in the Gly genotype only salbutamol response was significant. However when comparing the Arg vs. Gly genotypes there were no significant differences for any of the outcomes. <h3>Conclusion</h3> Propranolol produces significant effects on pulmonary function and salbutamol response in the Arg genotype, although there were no significant differences between Arg and Gly genotypes.
Intense Splenic 99mTc-MDP Uptake in a Patient With Myelofibrosis
Authors: Ming Chen, Chun Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2013)

99mTc-MDP bone scan was performed in a 49-year-old woman with breast cancer. Whole-body bone scan showed multiple foci of increased MDP activity in the bone and intense splenic 99mTc-MDP uptake. Initial bone marrow aspiration in multiple locations yielded no blood cells. A subsequent bone marrow biopsy in the left anterior superior iliac spine showed myelofibrosis in addition to the known bone metastasis.