tbuckley/cabot-search huggingface dataset:
Abstract 978: Novel Endothelial-protective Effect of High Density Lipoprotein: Down-regulation of Toll-like Receptor 4
Authors: Frank Spillmann, Sophie Van Linthout, Aysun Subasigüller, Carola Bücker-Gärtner, Meloni Meloni, Marina Egorova, Bart De Geest, Heinz-Peter Schultheiss, Carsten Tschöpe
Journal: Circulation (2007)

Introduction: Endothelium-derived Toll-like receptor (TLR) 4 is known to be the key molecule in lipopolysaccharide (LPS)-induced neutrophil sequestration into lungs. The aim of our study was to investigate whether the endothelial-protective effects of HDL also include regulation of Toll-like receptor (TLR) 4. Therefore, we analyzed the effect of HDL supplementation on TLR4 expression in human aortic endothelial cells (HAEC) and the effect of increased HDL following adenoviral apo AI ( Ad.AI) gene transfer (GT) on lung TLR4 expression in an experimental model of LPS-induced endotoxic shock. Methods: HDL (50 μg/ml) was supplemented to HAEC in the presence/absence of LPS (100 ng/ml). Surface-TLR4 expression on HAEC was analyzed by FACS. C57BL/6 mice were i.v. injected with 5 x 10 10 total particles of Ad.AI or with Ad.Null . Fourteen days hereafter, mice were i.p. injected with LPS (80 mg/kg) or with saline and 20 hours afterwards sacrificed. For survival studies, endotoxic shock was induced in 25 mice per group. Lung myeloperoxidase activity (MPO), as a marker of neutrophil infiltration was analysed. Lung TLR4-mRNA expression was determined by real-time PCR, plasma interferon-gamma (INFγ) levels by ELISA. Results: HDL supplementation significantly reduced TLR4 expression on HAEC. Ad.AI resulted in human apo AI expression levels of 80 ± 10 mg/dl at day 14. By 24 hours after LPS injection, 81% of LPS-treated Ad.Null and saline mice died, in contrast to 50% of Ad.AI LPS-treated mice. This was associated with a 1.6- and 1.7-fold (p&lt;0.05) lower lung/body weight ratio in Ad.AI compared to Ad.Null and saline LPS-injected mice. LPS-induced lung TLR4 mRNA expression was 2.0-fold (p&lt;0.05) reduced after human apo AI-GT compared to LPS controls. Moreover, human apo AI-GT significantly reduced neutrophil infiltration in LPS-treated mice, as indicated by 1.8-fold (p&lt;0.05) and 1.9-fold (p&lt;0.05) reduced MPO activity compared to controls, respectively. Plasma INFγ-levels were 2.8-fold and 2.2-fold (p&lt;0.05) lower versus LPS-treated Ad.Null and saline mice, respectively. Conclusion: The HDL-mediated reduction in lung TLR4 expression contributes for the reduced neutrophil infiltration and subsequently may account for improved mortality rate.
SCH66336 (Sarasar®), an oral farnesyl transferase inhibitor, synergizes with temozolomide and radiation therapy for orthotopic malignant gliomas
Authors: Jessica W. Barnes, Claire Sauvageot, Naren Ramakrishna, Jamie L. Dellagatta, Deviney Chaponis, Patrick Wen, Charles Stiles, Andrew Kung, Mark W. Kieran
Journal: Cancer Research (2006)

3798  Background: Malignant gliomas are highly lethal tumors that display resistance to current therapies. The best treatment modality currently available for these tumors is a combination of maximal surgical resection followed by radiation therapy and concurrent temozolomide, an oral alkylating imidazotetrazine derivative. Although this combination has demonstrated activity, development of resistance and disease progression is common. Thus, additional agents to augment the effectiveness of this approach are needed. The presence of increased Ras signaling in malignant glioma offers a potential novel target. We now report the in vitro and orthotopic in vivo results of combination therapy using irradiation, temozolomide and SCH66336, an oral farnesyl transferase inhibitors, in a murine model of glioblastoma multiforme (GBM). Methods: To examine the activity of radiation, temozolomide, and SCH66336 U87 in vitro and in U87-induced intracranial tumors in SCID or nude mice were evaluated following treatment combinations. Experimental regimens included vehicle control, radiation and temozolomide (2.5Gy/day for 2 days, 5mg/kg/day 90 min prior to radiation), or SCH66336 (80 mg/kg SCH66336 by oral gavage once daily) alone and in combination with SCH66336. Endpoints evaluated included cell number, proliferation index, apoptotic index, and Ras activation. After completion of the experiment (defined as control or treated animals with symptomatic disease), animals were evaluated by MRI (T1, T2, T1 + gadolinium), sacrificed, and the brains perfused. Sections (5um) including tumor and adjacent brain were prepared and stained for CD31, Ki67 and an apoptotic marker. Results: As previously reported, radiation and concurrent temozolomide can induce significant cellular damage as demonstrated by proliferation inhibition and apoptosis. Similarly, SCH66336 independently inhibited Ras pathway signaling as determined by the activity of Ras isotypes and activation of downstream targets. SCH66336 alone had limited ability to inhibit orthotopic U87 tumors (T/C of 0.67), while the combination of radiation and temozolomide produced significant inhibition (T/C of 0.42). With concurrent SCH66336, radiation, and temozolomide, a decrease in T/C of 0.02 was observed with the majority of animals demonstrating a decrease in tumor volume (p
Abstract 2097: National Survey of Cardiologists’ Perceptions of Continuous ST-segment Monitoring
Authors: Kristin E Sandau, Sue Sendelbach, Joel Frederickson, Karen Doran
Journal: Circulation (2008)

Continuous ST-segment (cST-seg) monitoring has been shown to help identify early and transient cardiac ischemia. American Heart Association and American Association of Critical Care Nurses recommend its use among specific patient populations. Investigators examined factors associated with cardiologists’ reported benefits, barriers, and perceptions of usefulness for cST-seg monitoring. A random sample (n=200) within a national pool of 4,985 cardiologists registered with the vendor Epocrates® was electronically surveyed. Cardiologists agreed/ strongly agreed that benefits of cST-seg monitoring included early identification of potential ischemia (83.5%), and early identification of reocclusion after PCI (74%) or fibrinolytics (72.5%). Cardiologists agreed/strongly agreed that barriers included false positive alarm for ischemia (61.5%); lack of understanding of this technology by nursing staff (56.5%); extra phone calls based on inaccurate monitoring (48%); lack of understanding of this technology by other physicians (47%); and extra cost/ treatment due to false positive alarms (43%). Cardiologists agreed/strongly agreed that cST-seg monitoring identifies patients who need further tests (69%) and is clinically useful in detecting transient myocardial ischemia (65%). The primary factor associated with higher benefits, clinical usefulness, and past use of cST-seg monitoring by cardiologists was whether or not their hospitals had a standard of practice for using cST-seg monitoring. The secondary factor was awareness of published consensus guidelines for cST-seg monitoring. Findings may indicate that when cardiologists are given the opportunity to work with a hospital that provides guidelines and experience in cST-seg monitoring, they may be more likely to appreciate its benefits and clinical utility. Clinical leaders should initiate multi-disciplinary efforts to review the level of evidence for possible incorporation of cST-seg monitoring into their hospitals’ standards of practice. Findings will help direct further research and interdisciplinary education in appropriate use of technology by critical care nurses and cardiologists.
Abstract 11422: Coupling Factor 6 Accelerates Aging and Shortens Lifespan Through Reduced Autophagy by Proton-Mediated Histone Acetylation
Authors: Tomohiro Osanai, Kei Izumiyama, Akiko Suzuki, Makoto Tanaka, Hirofumi Tomita, Akihiro Kobayashi, Ken Okumura
Journal: Circulation (2013)

Backgrounds: Proton regulates cellular functions by modulating the charge and structure of macromolecules, but its role in aging is unknown. We recently identified a circulating peptide coupling fa...
Abstract P397: Twenty-year Trends of Treatment and Control for Elevated Serum Cholesterol among Minnesota and U.S. Adults
Authors: Lyn M Steffen, Xia Zhou, David R Jacobs, Henry Blackburn, Russell V Luepker
Journal: Circulation (2012)

Background: We recently reported lower CHD mortality rates and risk factor levels between 1980 and 2000 in Minnesotans compared to the general US population. Here we report the trends for treatment and control of elevated serum total cholesterol (TC). Methods: Cross-sectional surveys were conducted in men and women aged 25-74 years in the Minnesota Heart Survey (MHS) from 1990 to 2009 and in the National Health and Nutrition Examination survey (NH) from 1988 to 2008, in which height, weight, and medication use were obtained and TC measured. A single generalized linear mixed model was used to estimate age-adjusted and gender-specific linear trends of TC and of treatment and control of high TC in MHS and NH taking into account the complex sampling strategy as random effects, (i.e., neighborhood or strata and primary sampling unit pairings). Differences (pdiff) were calculated for slope and TC between surveys. Results: Between 1990 and 2008-09, percent obese increased. TC declined at the same rate in MHS and NH men and women, but TC levels were lower in MHS (pdiff0.05). TC was generally lower in MHS men and women compared to NH for each treatment and control category. Conclusion: Although TC levels have declined over the past several decades in both regional and national populations, the prevalence for untreated and treated but uncontrolled high TC remains high at 38% in MHS and 46% in NH. Findings were more favorable for Minnesotans than nationally. 20-Year Trends of Serum Cholesterol Treatment and Control in Men and Women: MHS vs. NHANES Untreated/ Controlled (%) Untreated/ Uncontrolled (%) Treated/ Controlled (%) Treated/ Uncontrolled (%) Year * MHS NH MHS NH MHS NH MHS NH Men 1991 41.9 40.7 35.4 36.9 6.0 3.8 16.8 18.5 1996 ** 39.1 38.3 36.0 35.7 6.3 8.1 18.6 17.8 2001 38.4 40.3 31.4 31.9 12.2 8.8 18.0 19.0 2008 40.6 39.1 21.2 30.7 22.0 16.3 16.1 13.9 Ptrend 0.32 0.36 &lt;=0.001 0.001 &lt;0.001 &lt;0.001 0.56 0.03 Pdiff p=0.90 p=0.001 p=0.005 p=0.20 Women 1991 48.7 42.9 30.1 34.8 4.2 3.4 17.0 18.9 1996 45.9 39.3 30.7 34.3 5.9 5.6 17.5 20.8 2001 47.0 43.9 27.7 32.8 6.8 5.9 18.4 17.5 2008 48.1 40.9 23.9 27.9 12.8 12.7 15.2 18.5 ptrend 0.86 0.25 &lt;0.001 &lt;0.001 &lt;0.001 &lt;0.001 0.21 0.73 pdiff p=0.45 p=0.86 p=0.91 p=0.52 Controlled total cholesterol=less than 200 mg/dL, Uncontrolled total cholesterol= greater than or equal to 200 mg/dL MHS=Minnesota Heart survey; NH=NHANES * Midpoint of survey time period ** Survey year for NHANES was 1999
乳癌患者のためのドセタキセル誘発爪甲離床症および皮膚毒性を防ぐ凍結手袋の多施設第II相研究(Kinki Multidisciplinary Breast Oncology Group: KMBOG-0605)
Authors: Masuda N, Nakayama T, Ishitobi M, Masuda H, Yamamura J, Fujino M, Fujii C, Iseki C, Ueno H, Sakurai M, Todaka K, Takada N, Kamigaki S, Anami S, Shikata A
Journal: Cancer Research (2009)
Abstract 646: Dual-modal Biophotonic Imaging of the Canine Sino-Atrial Nodal Structure and Function
Authors: Vadim V Fedorov, Richard B Schuessler, William J Hucker, Christina M Ambrosi, Kelley V Foyil, Crystal M Ripplinger, Igor R Efimov
Journal: Circulation (2007)

The origin of a canine heart beat is hidden from epi- or endocardial mapping due to slow impulse propagation within the sinoatrial node (SAN) before its atrial breakthrough. Thus, the relation betw...
Abstract 16407: Mir-145 is Differentially Regulated by Tgf{beta}1 and Ischemia and Targets Disabled-2 Expression and Wnt/{beta}-Catenin Activity in Myocardium and Mesenchymal Stem Cells
Authors: Mary E Mayorga, Marc S Penn
Journal: Circulation (2011)

Introduction: The effect of wnt/β-catenin signaling in the response to acute myocardial infarction (AMI) remains controversial. Studies have suggested that wnt/β-catenin signaling affects cardiac s...
Abstract 4415: The Utility of Genotyping in the First Evaluation of a Novel Vitamin K Antagonist: ATI-5923
Authors: Michael D Ezekowitz, Peter Milner, Dave Ellis, M. Haris U Usman, Daniel M Canafax, Pascal Druzgala
Journal: Circulation (2008)

(S)-Warfarin, the most active enantiomer of warfarin, is metabolized by CYP2C9. Genetic variations of the CYP2C9 gene result in slower metabolism and are major contributors to inter-patient dose variability with resultant INR instability, especially in patients on multiple medications. This leads to higher hemorrhagic and thrombotic complications. ATI-5923 (ARYx therapeutics Inc.) is a novel VKOR inhibitor that undergoes metabolism by human carboxyles-terase and not by CYP2C9. We hypothesize that time in therapeutic range (TTR) based on Rosendaal method is better for ATI-5923 than for historic warfarin and that maintenance dose is independent of CYP2C9 polymorphism, but dependent on VKOR haplotype. This was a multi-center, open-label, 3 month study of 66 patients with AF treated with ATI-5923. All except two patients were on prior warfarin. Periodic INR testing occurred twice weekly for the first 3 weeks and then weekly during the maintenance phase. Genetic testing for the CYP2C9 and VKORC1 polymorphism was performed on all patients. Drug dosing was performed using a standardized nomogram. Pre-study INRs and warfarin dose data were collected for up to one year prior to study entry. 77 % of patients were in therapeutic range (INR 2–3) after 7 days and 80% had stable INR (3 consecutive INR values within range without dose adjustment) by 3 months. For the maintenance phase the mean TTR was 71.5 and 59.3% for ATI-5923 and warfarin respectively (12.2% improvement; p=0.0009). Patients with the VKOR AA haplotype required lower maintenance doses than VKOR GA or GG haplotype (8.6 vs 15.8 and 18.7mg; p &lt; 0.0001). CYP2C9 genotype had no influence on maintenance dose. CYP2C9 variants (n=20), showed a trend toward better control compared to warfarin; 16% improvement vs. 11% for wild type CYP2C9 (n =42). ATI-5923 has better INR control than prior warfarin therapy. VKOR AA patients require a significantly lower maintenance dose. CYP2C9 variants show a trend to added improvement compared to the CYP2C9 wild type, suggesting that, unlike warfarin, ATI-5923 is not influenced by CYP2C9 genetic variations.
Abstract 2328: Rapamycin Withdrawal versus Delayed Initiation: Thrombosis vs. Suppression of Neointimal Hyperplasia after Vascular Injury
Authors: Mitesh V Badiwala, Elissa D Tepperman, Rohit Sheshgiri, Jessica L Prodger, Laura C Tumiati, Diego H Delgado, Heather J Ross, Vivek Rao
Journal: Circulation (2008)

Objectives Current clinical strategy to delay progression of established cardiac allograft vasculopathy (CAV) following transplantation includes the use of rapamycin. We examined the effect of dela...
Abstract 2052: A Rapid Cooling of The Brain Using Percutaneous Cardiopulmonary Bypass Significantly Improves Neurological Function in Patients with Out-of-Hospital Cardiogenic Cardiac Arrest
Authors: Hitoshi Kano, Tomoyuki Satou, Kei Yamazaki, Tomoyo Saitou, Akio Endou, Hidekazu Shimojima, Shuuhei Takauji, Masahide Akita, Hiroshi Nakayama, Toshihisa Matsui, Masaki Okada, Hiroshi Makise, Yuuta Nakagawa, Takao Makino, Naoki Iwakiri, Hiroyuki Fukuda, Noriyoshi Katou, Masaki Togashi, Tetsunori Yoshida
Journal: Circulation (2008)

Objectives: Neurological recovery in patients (pts) with out-of-hospital cardiogenic cardiac arrest (OHCCA) is affected by the cerebral circulatory collapse time from the cardiac arrest to the return of spontaneous circulation. According to recent studies, the cerebral circulatory collapse time is estimated to be 30 min. or less in order to successfully recover neurologically. In addition, percutaneous cardiopulmonary bypass (PCPB) is a powerful tool for rescuing the pts with OHCCA refractory to advanced cardiovascular life support (ACLS), and we have been positively performing cardiopulmonary cerebral resuscitation and rapidly cooling of the brain using PCPB. In this treatment, the cerebral circulatory collapse time is the duration from cardiac arrest to the start of PCPB, we discovered the fact that there are many neurologically successful cases of recovery even though the cerebral circulatory collapse time has exceeded 30 min. In the present study, we investigated the neurological prognosis in relation to the cerebral circulatory collapse time. Methods: From January 2006 to April 2008, 77 consecutive pts with OHCCA, who have been treated with brain hypothermia at 34 degree C were included. 77 pts were divided into two groups. Brain hypothermia (BH) groups (n=34) were treated with only brain hypothermia after the return of spontaneous circulation, and PCPB groups (n=33) were treated with hypothermia using PCPB against refractory to ACLS. The relation between the cerebral circulatory collapse time and the neurological prognosis were assessed. Results: The cerebral circulatory collapse time were from 8 min. to 78 min. in the BH groups, whereas it lasted from 22 min. to 91 min. in PCPB groups. In BH groups, the cases with the favorite neurological outcome were 23 cases (67.6%) and the average collapse time was 19.2 min. (8 to 35 min.) In contrast, in the PCPB groups, the successful neurological cases were 15 cases (45.5%), the average collapse time was 43.6 min (22 to 60 min.) In the cases who received PCPB, there were cases of neurologically successful prognoses even though the cerebral circulatory collapse time was long. Conclusions: These results suggest that a rapid cooling of the brain using PCPB permits a cerebral circulatory collapse time.
Abstract 1144: Complete Revascularization of Patients Undergoing Multivessel PCI is an Independent Predictor of Improved Long-Term Survival
Authors: Ralf Lehmann, Laura Held, Carola Hobler, Gregor Baier, Stephan Fichtlscherer, Volker Schaechinger, Andreas M Zeiher, Ioakim Spyridopoulos
Journal: Circulation (2008)

The prognostic relevance of completeness of revascularization (CR) in patients with coronary multivessel disease (MV-CAD) has so far only been established for surgical treatment strategies. Therefore we investigated the prognostic impact of CR in patients with CAD undergoing multivessel PCI (MV-PCI). Long-term survival was assesed in 679 consecutive patients (pts), who underwent MV-PCI. 47% were treated for acute myocardial infarction. We adapted two common definitions of CR from the CABG trials for our study population: ARTS -successful treatment of all relevant lesions; BARI - no residual stenosis in the LAD. CR according to the ARTS definition was achieved in 73% of the stable patients as compared to only 61% in acute pts. CR (BARI) was achieved in 95% of all pts. Patients with CR demonstrated a better long-term survival (see figure ). Using a multivariable cox regression analysis, procedural factors such as left main PCI, number of diseased vessels, number of treated lesions, number of stents, total stent length, and acuity of underlying CAD did not predict survival. Independent predictors (p&lt;0.05) of long-term mortality were age (&gt; 60y HR 2.36), reduced LVEF (LVEF&lt;40% HR 3.44), female gender (HR 1.67), chronic renal failure (creatinine &gt; 200 mmol/l HR 2.68), elevated CRP (HR 2.09) as well as CR (ARTS; HR 0.46). An open LAD after procedure and PCI on at least one additional vessel (BARI) did not independently predict improved survival. Achievement of CR of all segments is associated with improved survival after PCI in pts with multivessel disease, regardless of the indication for PCI (acute MI or stable CAD).
Ulcerative Colitis
Authors: A. P. Dick, M. J. Grayson
Journal: BMJ (1961)

I % 4 ~~~~~~~~~~MD I C A L JOURNqAL Summary During the last few years it has proved possible to recognize a group of patients with ulcerative colitis in whom removal of milk and protein-containing milk products from the diet has been followed by marked improvement in the clinical course of the illness.In five of these patients milk has been reintroduced into the diet, and on every occasion this has been followed in a few days or weeks by a frank attack of ulcerative colitis.One patient was tested twice on separate occasions, so that there were six such events in all.From previous studies in which patients in clinical remission were being treated with "dummy" tablets, it is possible to arrive at an estimate of the risk of spontaneous relapse in a patient with ulcerative colitis.Taking an outside figure for this risk, it can be shown that it was very unlikely that the six relapses would have occurred by chance alone.In other words, there was almost certainly a causal connexion between the reintro- duction of milk into the diet and the subsequent relapse.There was a highly significant positive correlation between the time a patient was symptom-free while on a milk-free diet and the time taken to clinical relapse after reintroduction of milk into the diet.This finding is compatible with the notion of these relapses repre- senting an immunological type of response to milk proteins, with the reactivity of the colonic mucosa varying according to the length of time since it was last exposed to the allergen.
Document is worrying
Authors: Philip R Matthews
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. cnri/spl Acute bronchiolitis risk of hyponatraemiaBush and Thomson stated that electrolytes should be determined only in infants with bronchiolitis who are dehydrated. 1 However hyponatraemia is seen in up to 33% of children in hospital with this disease. 2It is unrelated to dehydration and has been associated with administration of intravenous fluids together with increased antidiuretic hormone values. 3 4 It can cause generalised tonic-clonic seizures, 2 which may be refractory to anticonvulsants.The National Patient Safety Agency has issued an alert aimed at reducing the risk of hyponatraemia in children -electrolytes should be determined before starting intravenous fluids and at least daily afterwards. 5 Fluids should be restricted in children with hyponatraemia who are receiving intravenous 0.9% saline (with 5% dextrose) and who have high antidiuretic hormone concentrations.