tbuckley/cabot-search huggingface dataset:
Subsequent brain tumors in patients with autoimmune disease
Authors: K. Hemminki, X. Liu, A. Forsti, J. Ji, J. Sundquist, K. Sundquist
Journal: Neuro-Oncology (2013)

Previous studies have reported increased risk of brain tumors after allergic conditions, but no systematic analyses of these tumors in patients with autoimmune disease (AId) have been performed. No data are available on survival among patients with AId from brain tumors. We analyzed systematically risks and survival in histological types of brain tumors among patients who received a diagnosis of 33 different AIds. Standardized incidence ratios (SIRs) for brain tumors or hazard ratios (HRs) of deaths after brain tumors were calculated up to 2008 in 402 462 patients hospitalized for AId after 1964 and were compared with data on the population not hospitalized for AIds. Brain tumors were diagnosed in 880 patients with AId. No increased or decreased risks (SIRs) were noted for glioma, whereas the increased SIRs for meningioma after many AIds were likely to be attributable to surveillance bias. The data on survival showed overall decreases for glioma (HR, 1.15) and meningioma (HR, 1.26). The survival in both was decreased in patients with chronic rheumatic heart disease, multiple sclerosis, and rheumatoid arthritis. Overall, HRs were increased for glioma after 6 AIds and for meningioma after 7 AIds. The present data showed that none of the 33 AIds influenced the risk of glioma. However, many AIds negatively influence survival in glioma and meningioma, probably through added physical burden or therapeutic limitations. Information of an existing AId in patients with newly diagnosed brain tumors should help the prognostic assessment and the design of treatment.
Spontaneous regression of a giant pulmonary bulla.
Authors: D. A. Bradshaw, K. M. Murray, D. E. Amundson
Journal: Thorax (1996)

Gradual expansion of a lung bulla is common and may be associated with debilitating pulmonary symptoms. The aetiology of bulla expansion is unclear. Spontaneous regression, on the other hand, is rarely observed. The case is presented of a man in whom near complete spontaneous resolution of a giant pulmonary bulla occurred. This event was associated with dramatic improvement in the radiographic picture and pulmonary function.
A method for generating obstructive thrombi in the coronary arteries of the conscious dog
Authors: I. HAYASHI, T. WASFIE, P. FREED, M. EKSTROM, J. POLANSKI, H. YOSHIZU, A. STEIN, A. KANTROWITZ
Journal: Cardiovascular Research (1983)

A technique for staging the generation of obstructive thrombi in the coronary arteries of conscious dogs is described. At thoracotomy, electrodes are placed in the lumina of coronary artery branches. When thrombus generation in proximity to the intraluminal electrode tip is desired, anodal current is applied to the exteriorised end of the electrode. In each of nine anaesthetised adult mongrel dogs two to seven intracoronary electrodes were implanted for a total of 35. One to 75 days later, 50 to 800 microA anodal current was applied to 16 electrodes for 30 min to 48 h. Upon autopsy, thrombi in various stages of organisation were found in proximity to the intracoronary portion of 15 electrodes. Six electrodes were found to be damaged or broken. In contrast, only four of the 13 control electrodes were sites of thrombus formation. In seven dogs tissue sections indicated either myocardial ischaemia or infarct in regions whose perfusion was blocked by thrombi. This method may provide for discretionary generation of intracoronary thrombi in the desired quantity, at the preferred site(s), at selected times of onset. Consequently, it offers the possibility of adjusting the onset, severity, and time course of myocardial ischaemia.
Mortality and morbidity in gastro-oesophageal cancer surgery: initial results of ASCOT multicentre prospective cohort study
Authors: P. McCulloch
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effect of comorbidity and other risk factors on postoperative mortality and morbidity in patients undergoing major oesophageal and gastric surgery. <b>Design</b> Multicentre cohort study with data on postoperative mortality and morbidity in hospital. <b>Data source and methods</b> The ASCOT prospective database, comprising 2087 patients with newly diagnosed oesophageal and gastric cancer in 24 hospitals in England and Wales between 1 January 1999 and 31 December 2002. Multivariate logistic regression analysis was used to model the risk of death and postoperative complications. <b>Results</b> 955 patients underwent oesophagectomy or gastrectomy. Of these, 253 (27%) were graded ASA III or IV, and 187 (20%) had a high physiological POSSUM score (≥ 20). Operative mortality was 12% (111/955). Physiological POSSUM score, surgeon9s assessment, type of operation, hospital case volume, and tumour stage independently predicted operative mortality. Medical complications were associated with higher physiological POSSUM scores and ASA grade, oesophagectomy or total gastrectomy, thoracotomy, and radical nodal dissection. Stage and additional organ resection predicted surgical (technical) complications. <b>Conclusions</b> Many patients undergoing surgery for gastro-oesophageal cancer have major comorbid disease, which strongly influences their risk of postoperative death. Technical complications do not seem to be influenced by preoperative factors but reflect the extent of surgery and perhaps surgical judgment. Detailed prospective multicentre cooperative audit, with appropriate risk adjustment, is fundamental in the evaluation of cancer care and must be properly resourced.
Estimation of Vmax in auxotonic systoles from the rate of relative increase of isovolumic pressure: (dP/dt)kP
Authors: Michael J. Wolk, John F. Keefe, Oscar H. L. Bing, Lawrence J. Finkelstein, Herbert J. Levine
Journal: Journal of Clinical Investigation (1971)

High speed oscilloscopic recordings (4000 mm/sec) of left ventricular pressure (micromanometer) and its first derivative were used to calculate contractile element velocity (Vce) during the isovolumic period of auxotonic beats in anesthetized dogs. At 0.5-2.0 msec intervals of isovolumic systole, Vce was derived as (dP/dt)/kP, where k = 24 cm(-1). Plots of Vce and P yielded inverse curves from peak Vce to aortic valve opening pressure which averaged 27 msec in controls, and 11 msec during norepinephrine administration. Extrapolated Vmax, in muscle lengths/second, averaged 3.6 (controls), 3.6 (volume load), and 6.6 (norepinephrine). In each experimental state, Vmax was also determined from force-velocity relations of isovolumic beats (abrupt aortic occlusion) analyzed at 10 msec intervals from conventional pressure recordings. Vmax by both methods correlated well (r = 0.88). While good correlations were also noted between Vmax and maximum dP/dt, (max dP/dt)/integrated isovolumic pressure, (max dP/dt)/peak isovolumic pressure, and (max dP/dt)/kP, only the last two of these successfully distinguished changes between volume load and inotropic stimulation. Thus, assuming an unchanged series elasticity, the contractile state of the auxotonic ventricle may be determined utilizing a single high-fidelity catheter system and high speed recordings of isovolumic pressure.
Farnesyl and Geranylgeranyl Transferase Inhibitors Induce G1 Arrest by Targeting the Proteasome
Authors: Ekem T. Efuet, Khandan Keyomarsi
Journal: Cancer Research (2006)

Abstract Isoprenoid inhibitors are being evaluated as agents for the treatment of cancer. Their antitumor activity is attributed to inhibition of post-translational modification of Ras, which is crucial for its translocation and attachment to the plasma membrane, and ultimate involvement in signal transduction. However, whether blocking of Ras is solely responsible for the observed antitumor activity is unresolved. In this report, we propose an alternate mechanism. Using breast tumor models, we show that agents possessing a lactone moiety, including statins (such as lovastatin) and the isoprenoid inhibitors (such as FTI-277 and GGTI-298), mediate their cell cycle inhibitory activities by blocking the chymotrypsin activity of the proteasome in vitro. This results in the accumulation of cyclin-dependent kinase inhibitors p21 and p27 with subsequent G1 arrest. Cells devoid of p21 were refractory to the growth-inhibitory activity of lovastatin, FTI-277, and GGTI-298. However, in these p21 null cells, isoprenylation of key substrates of farnesyl transferase (such as Ras) and of geranylgeranyl transferase (such as RAP-1) were inhibited by FTI-277 and GGTI-298, respectively, suggesting that although both these isoprenoid inhibitors reached and inhibited their intended targets, inhibition of the isoprenylation of Ras and RAP-1A are not sufficient to mediate G1 arrest. We also show that the cell cycle effects can be attributed to the functional lactone moiety of the aforementioned agents. Collectively, our data suggest that FTI and GGTI and other agents containing an active lactone moiety mediate G1 arrest via inhibition of the proteasome and up-regulation of p21, independent of the inhibition of isoprenylation of Ras or RAP-1. (Cancer Res 2006; 66(2): 1040-51)
CHLORPROPAMIDE-INDUCED LEUCINE HYPOGLYCEMIA*
Authors: C. Lucas, G. Reaven
Journal: Journal of Clinical Investigation (1963)

Previous reports from this laboratory have demonstrated that L-leucine-induced hypoglycemia can be experimentally produced in normal dogs dur- ing periods of either exogenous (1) or endoge- nous (2) hyperinsulinism.On the basis of these experiments, it was suggested that L-leucine acts to inhibit hepatic glucose output and that "leucine hypoglycemia" occurs in situations where increased hepatic glucose output is necessary for maintenance of euglycemia.To extend these observations of experimental leucine hypoglycemia, it seemed de- sirable to investigate the effect of L-leucine in other situations characterized by hypoglycemia, hyperinsulinism, or both.Consequently, we have measured the blood glucose response to L-leucine at varying intervals after both the acute and chronic administration of chlorpropamide.1In addition, we have attempted to ascertain in con- trolled experiments whether or not L-leucine by itself has any effect on blood glucose concentra- tion.Finally, we have attempted to demonstrate that L-leucine inhibits hepatic glucose output by comparing hepatic-vein-femoral-vein (HV-FV) blood glucose concentration differences in dogs.with and without pretreatment with chlorpropamide. METHODSA. Effect of L-leucine on peripheral blood glucose con- centration with and without chlorpropantide pre- treatment Nine mongrel dogs were used in these experiments, and the hypoglycemic response to L-leucine was tested in each dog under all five of the following experimental conditions: 1) 2 hours, 2) 12 hours, and 3) 24 hours af-
Sinusoidal endothelial cells direct traffic at the intersection of regeneration and fibrosis
Authors: Robert C. Huebert, Vijay H. Shah
Journal: Hepatology (2014)

Abstract Chemical or traumatic damage to the liver is frequently associated with aberrant healing (fibrosis) that overrides liver regeneration. The mechanism by which hepatic niche cells differentially modulate regeneration and fibrosis during liver repair remains to be defined. Hepatic vascular niche predominantly represented by liver sinusoidal endothelial cells deploys paracrine trophogens, known as angiocrine factors, to stimulate regeneration. Nevertheless, it is not known how pro-regenerative angiocrine signals from liver sinusoidal endothelial cells is subverted to promote fibrosis. Here, by combining an inducible endothelial-cell-specific mouse gene deletion strategy and complementary models of acute and chronic liver injury, we show that divergent angiocrine signals from liver sinusoidal endothelial cells stimulate regeneration after immediate injury and provoke fibrosis after chronic insult. The pro-fibrotic transition of vascular niche results from differential expression of stromal-derived factor-1 receptors, CXCR7 and CXCR4 in liver sinusoidal endothelial cells. After acute injury, CXCR7 upregulation in liver sinusoidal endothelial cells acts with CXCR4 to induce transcription factor Id1, deploying pro-regenerative angiocrine factors and triggering regeneration. Inducible deletion of Cxcr7 in sinusoidal endothelial cells (Cxcr7 iΔEC/iΔEC ) from the adult mouse liver impaired liver regeneration by diminishing Id1-mediated production of angiocrine factors. By contrast, after chronic injury inflicted by iterative hepatotoxin (carbon tetrachloride) injection and bile duct ligation, constitutive FGFR1 signaling in liver sinusoidal endothelial cells counterbalanced CXCR7-dependent pro-regenerative response and augmented CXCR4 expression. This predominance of CXCR4 over CXCR7 expression shifted angiocrine response of liver sinusoidal endothelial cells, stimulating proliferation of desmin + hepatic stellate-like cells and enforcing a pro-fibrotic vascular niche. Endothelial-cell-specific ablation of either Fgfr1 (Fgfr1 iΔEC/iΔEC ) or Cxcr4 (Cxcr4 iΔEC/iΔEC ) in mice restored the pro-regenerative pathway and prevented FGFR1-mediated maladaptive subversion of angiocrine factors. Similarly, selective CXCR7 activation in liver sinusoidal endothelial cells abrogated fibrogenesis. Thus, we demonstrate that in response to liver injury, differential recruitment of pro-regenerative CXCR7-Id1 versus pro-fibrotic FGFR1-CXCR4 angiocrine pathways in vascular niche balances regeneration and fibrosis. These results provide a therapeutic roadmap to achieve hepatic regeneration without provoking fibrosis.
Recognition of viral glycoproteins by influenza A-specific cross-reactive cytolytic T lymphocytes.
Authors: U H Koszinowski, H Allen, M J Gething, M D Waterfield, H D Klenk
Journal: The Journal of Experimental Medicine (1980)

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized.
PTU-048 The Effect of the Colonoscope Magnetic Imaging Device (Scopeguide ®) on Implantable Cardiac Devices: Abstract PTU-048 Table 1
Authors: G D Corbett, Y C Lim, P Pugh, E Cameron
Journal: Gut (2013)

<h3>Introduction</h3> Use of the colonoscope magnetic imaging device (ScopeGuide®, Olympus) is currently contraindicated by the manufacturer for patients with implantable cardiac devices. This group of patients is increasing every year, as is the number of colonoscopies being performed. This is the first study which examines the safety of ScopeGuide® in patients with permanent pacemakers (PPMs), implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT). <h3>Methods</h3> Before any patient experiments, ex-vivo proof of concept studies were performed. Non-implanted devices were exposed to the electromagnetic field (EMF) of ScopeGuide® and monitoring demonstrated no evidence of interference or change in settings. Following this, ethical approval was obtained and consecutive patients attending device cheque clinics were prospectively recruited and exposed to ScopeGuide® EMF. After an initial device cheque, patients were attached to a device programmer and underwent continuous external cardiac monitoring. A colonoscope was placed curled on the abdomen over their clothing with patients lying supine to simulate the EMF generated during colonoscopy. The colonoscope was connected to ScopeGuide®. After 2 minutes of observation to assess for any interference, ScopeGuide® was disconnected and devices were checked for any change in settings. <h3>Results</h3> 143 patients were invited to participate and of these 70 were recruited to take part in the study (46 male, 24 females, mean age 68.5 years SD 10.3). Device type, indication and manufacturer are summarised in Table 1. No evidence of interference was seen on device leads nor was any change in programming detected following exposure to ScopeGuide® EMF in any patient. <h3>Conclusion</h3> The ScopeGuide® does not cause any interference or change in settings and appears to be safe to use in patients with implantable cardiac devices. <h3>Disclosure of Interest</h3> None Declared
Health-related quality of life of long-term high-grade glioma survivors
Authors: Ingeborg Bosma, Jaap C. Reijneveld, Linda Douw, Maaike J. Vos, Tjeerd J. Postma, Neil K. Aaronson, Martin Muller, W. Peter Vandertop, Ben J. Slotman, Martin J. B. Taphoorn, Jan J. Heimans, Martin Klein
Journal: Neuro-Oncology (2008)

The objective of this study was to compare the health-related quality of life (HRQOL) of long-term to short-term high-grade glioma (HGG) survivors, determine the prognostic value of HRQOL for overall survival, and determine the effect of tumor recurrence on HRQOL for long-term survivors. Following baseline assessment (after surgery, before radiotherapy), self-perceived HRQOL (using the Medical Outcomes Study Short Form 36 [SF-36]) and brain tumor-specific symptoms (using the 20-item Brain Cancer Module) were assessed every 4 months until 16 months after histological diagnosis. Kaplan-Meier survival analysis and the Cox proportional hazards model were performed to estimate overall survival of patients with impaired scores on the aggregated SF-36 higher-order summary scores measuring physical functioning on a physical component scale and on a mental component scale (MCS). Sixteen patients with a short-term survival (baseline and 4-month follow-up) and 16 with a long-term survival (follow-up until 16 months after diagnosis) were selected out of 68 initially recruited HGG patients. At baseline, the short-term and long-term survivors did not differ in their HRQOL. Between baseline and the 4-month follow-up, HRQOL of short-term survivors deteriorated, whereas the long-term survivors improved to a level comparable to healthy controls. Patients with impaired mental functioning (MCS) at baseline had a shorter median survival than patients with normal functioning. After accounting for differences in patient and tumor characteristics, however, mental functioning was not independently related to poorer overall survival. Not surprisingly, in the group of long-term survivors, the five patients with recurrence had a more compromised HRQOL at the 16-month follow-up compared to the 11 patients without recurrence. We concluded that baseline HRQOL is not related to duration of survival and that long-term survivors show improvement of HRQOL to a level comparable to that of the healthy.
A Modified T-Test Feature Selection Method and Its Application on the HapMap Genotype Data
Authors: Nina Zhou, Lipo Wang
Journal: Genomics Proteomics & Bioinformatics (2007)

Single nucleotide polymorphisms (SNPs) are genetic variations that determine the differences between any two unrelated individuals. Various population groups can be distinguished from each other using SNPs. For instance, the HapMap dataset has four population groups with about ten million SNPs. For more insights on human evolution, ethnic variation, and population assignment, we propose to find out which SNPs are significant in determining the population groups and then to classify different populations using these relevant SNPs as input features. In this study, we developed a modified t-test ranking measure and applied it to the HapMap genotype data. Firstly, we rank all SNPs in comparison with other feature importance measures including F-statistics and the informativeness for assignment. Secondly, we select different numbers of the most highly ranked SNPs as the input to a classifier, such as the support vector machine, so as to find the best feature subset corresponding to the best classification accuracy. Experimental results showed that the proposed method is very effective in finding SNPs that are significant in determining the population groups, with reduced computational burden and better classification accuracy.
PTH-072 A Retrospective Review of Video Capsule Endoscopy (VCE)
Authors: B Mustafa, L Langmead, M Samaan
Journal: Gut (2013)

<h3>Introduction Background</h3> Video capsule endoscopy (VCE) is one of the main investigations of the small bowel, especially in areas that cannot be examined by conventional endoscopy. VCE is considered gold standard for investigating obscure gastrointestinal bleeding and iron deficiency anaemia (IDA). <h3>Methods</h3> Patients who had VCE at our hospital over two separate periods of time were included. Case notes and VCE results were reviewed. In between the two time periods patency capsule became available at the hospital and new BSG guidelines for management of IDA were published. We compared the two time periods for indication with particular reference to adherence to the IDA guidelines, and capsule retention. <h3>Results</h3> 233 patients were identified, 48% (n = 111) male and 52% (n = 122) female. Median age (range) was 51 years (7- 94) with majority 30- 80 years. <h3>Indications</h3> IDA was the commonest indication for VCE (52.3%), followed by exclusion of inflammatory bowel disease (IBD) (21%). No difference was seen in referral patterns for IDA despite the IDA guidelines. <h3>Findings</h3> The most common finding overall was angioectasia (39.4%), of which 71% had IDA as indication. IBD was diagnosed in 4.2%. In cases of IDA, angioectasia was the most common finding (56%). There were no significant differences in findings between the two years studied. Non-steroidal anti-inflammatory drugs (NSAIDs) were more commonly used by patients referred with IDA (p = 0.009) but did not have an effect on the VCE result. Patency capsule was available only for the second period. It was performed in 22 (18.6% of referrals) cases. More than half of them were referred to investigate IBD; 11 VCEs were excluded on the basis of patency capsule result. The other 11 went on to have VCE. Capsule retention was documented in three cases overall (1.3%), one of them had prior patency capsule. Two of them passed the capsule without surgical intervention, and the third case was lost to follow up. <h3>Conclusion</h3> VCE is most commonly used to investigate obscure gastrointestinal bleeding and IDA. It is increasingly utilised for other indications such as diagnosis and assessment of IBD and coeliac disease. BSG guidelines for management of IDA recommend VCE only in certain groups of patients. We could significantly reduce VCE workload and resource requirements by adhering more closely to these guidelines. Patency capsule has opened the door to patients with potential strictures and probably increases opportunity to visualise the small bowel in Crohns disease particularly. However passage of the patency capsule does not 100% rule out VCE retention. <h3>Disclosure of Interest</h3> None Declared.